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Eur J Cardiothorac Surg 2002;21:995-1001
© 2002 Elsevier Science NL


Continuous monitoring of myocardial acid–base status during intermittent warm blood cardioplegia

A.C.L. Graffignaa*, G. Nollob, C. Pederzollia, P. Ferrarib, L. Widesottb, R. Antolinib

a Cardiac Surgery Unit, S. Chiara Hospital, Largo Medaglie d'Oro, 38100 Trento, Italy
b Department of Physics & ITC-IRST, University of Trento, Trento, Italy

Received 18 September 2001; received in revised form 9 January 2002; accepted 30 January 2002.

* Corresponding author. Tel.: +39-0461-903322; fax: +39-0461-903345
e-mail: graffigna{at}tn.aziendasanitaria.trentino.it


    Abstract
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 
Objective: Intermittent warm blood cardioplegia (IWBC) is a well-established technique for myocardial protection during cardiac operations. According to standardized protocols, IWBC administration is currently performed every 15–20 min regardless of any individual variable and in the absence of any instrumental monitoring. We devised a new system for continuous measurement of the acid–base status of coronary sinus blood for on-line evaluation of myocardial oxygenation during IWBC. Methods: In 19 patients undergoing cardiac surgery for coronary artery bypass graft and/or valve surgery and receiving IWBC (34–37°C) by antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every 15 min, continuous monitoring of myocardial oxygenation and acid/base status was performed by means of a multiparameter PO2, PCO2, pH, and temperature sensor (Paratrend7 ®, Philips Medical System) inserted into the coronary sinus. Results: Mean cross-clamping time was 76±26 min; ischemic time was 13±0.2 min. pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. After every ischemic period, the pH adaptation curve showed a complex pattern reaching step-by-step lower minimum levels (7.28±0.14 during the first ischemic period, to 7.16±0.19 during the third ischemic period – P=0.003). PO2 decreased rapidly at 90% in 5.0±1.2 min after every reperfusion. During ischemia, PCO2 increased steadily at 1.6±0.1 mmHg per minute, with progressively incomplete removal after successive reperfusion, and progressive increase of maximal level (42±12 mmHg during the first ischemic period, to 53±23 mmHg during the third ischemic period – P=0.05). Conclusions: Myocardial oxygen, carbon dioxide, and pH show marked changes after repeated IWBC. Myocardial ischemia is not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO2 and pH after each reperfusion. Progressive increase of reperfusion durations or direct monitoring of myocardial oxygenation could be advisable in cases of prolonged cross-clamping time.

Key Words: Cardiac blood pH • Myocardial protection • Cardioplegia


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 
Blood cardioplegia [1] is a consolidated technique for myocardial protection during cardiac operations, its validity being confirmed by several clinical trials [2].

Normothermic blood cardioplegia has been devised in the early 1980s [3,4] and described in clinical settings in the early 1990s [57], and is currently performed by administering an initial bolus and subsequent refracted doses. Although this behavior has been proved to be effective in providing adequate myocardial protection, no tools are commonly available for intra-operative monitoring of adequacy, and no definite patterns of the time course of myocardial acid–base state during warm blood cardioplegia are known.

The aim of this study was to perform continuous acid–base monitoring status of coronary sinus blood during cross-clamping, in order to evaluate the possibility of devising a control system of the property of myocardial protection.


    2. Materials and methods
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 
2.1. Surgery
From January to November 2001, 19 patients undergoing cardiac surgery for acquired cardiac disease were evaluated for continuous acid–base monitoring status of coronary sinus blood at the time of surgery (Table 1).


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Table 1. Demographic characteristics of the patientsa

 
Mean age of patients was 67±8 years (15 males). All patients were operated on with cardiopulmonary bypass at 34–37°C.

Intermittent warm blood cardioplegia (IWBC) was performed as described by Calafiore et al. [8]. Induction was obtained with a 3 min antegrade dose of oxygenated blood (300 cm3/min) with a potassium bolus of 6 mEq and a concentration of 20 mEq/l after that. Maintenance was obtained with 2 min doses, injection rate of 200 cm3/min, given every 10–20 min, and a potassium concentration of 16 mEq/l.

In coronary artery patients, maintenance doses were administered antegradely or retrogradely, the coronary sinus being anyway cannulated through the right atrium.

In aortic valve patients, maintenance doses were administered retrogradely, the coronary sinus being cannulated through the right atrium.

In mitral valve patients, maintenance doses were administered retrogradely, with the cardioplegic cannula directly inserted in the coronary sinus and secured by means of a purse-string suture.

2.2. Blood gases monitoring
Myocardial acid–base status was monitored by means of a probe (Paratrend7 ® – Philips Medical System), devised for arterial insertion, and with an external diameter of 0.50 mm. The probe consisted of four sensing elements measuring the optical absorption of dye sensitive to hydrogen ions (pH and PCO2), the amount of fluorescent light quenched by oxygen concentration (PO2), and finally a miniaturized thermocouple for temperature monitoring. The probe was brought to the operating field in a sterile sheath, and then connected to the coronary sinus cannula: directly, if antegrade maintenance doses were planned, or by means of a Y connector, if retrograde doses were planned. The probe tip was advanced 4–5 cm out of the coronary sinus cannula.

Fiberoptic filaments connected the sensing elements (Fig. 1 ). A microprocessor-based device (Trendcare ® – Philips Medical System) converted the electrical signals into digital data, allowing continuous data display, print, and transfer to personal computer for storage. Data were acquired and stored at a rate of one sample per second. Blood gases readings were corrected for the actual blood temperature.



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Fig. 1. Section view of the Paratrend7© probe (Philips Medical System) with pH, PO2, PCO2, and temperature sensor elements and tip dimensions.

 
The spontaneous changes of blood gases were evaluated at the end of the surgical procedure by continuous monitoring of pH, PO2, and PCO2 on oxygenated blood contained in a 20 cm3 syringe maintained at 36°C (Fig. 2 ).



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Fig. 2. Example of spontaneous deoxygenation of blood, left in a 20 cm3 syringe for 20 min.

 
2.3. Statistical analysis
Data were presented as the group means±the standard deviation. Unpaired Student's t-test was used to compare inter-group means, while paired Student's t-test was used to compare intra-group data. A P-value equal to or less than 0.05 was considered significant. Time was expressed as hh.mm.ss.


    3. Results
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 
Eight patients underwent valve and coronary artery surgery, five underwent isolated coronary artery surgery, and six underwent valve surgery. There were no operative deaths.

In 12 patients, cardioplegia doses were administered retrogadely and in seven patients antegradely. Mean cross-clamping time was 76±26 min, mean perfusion time per dose was 2.3±0.3 min, and mean ischemic time between doses was 13±0.2 min.

All patients received at least three cardioplegic doses, including the induction, 11 received four doses, five received five doses, and two received six doses. Due to this, all the results referring to the first three ischemic periods have been analyzed.

3.1. Coronary sinus pH
An example of the pH time course during subsequent cardioplegic/ischemic phases is reported in Fig. 3 . Relating data are reported in Table 2.



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Fig. 3. Tracing of the continuous monitoring of pH throughout the cross-clamping time as measured by the probe inserted in the coronary sinus. During each cardioplegic dose, pH decreased during every ischemic period in a non-linear fashion. Minimal values of pH were progressively lower in subsequent ischemic period. Data are relative to a patient (female, 79 years old) who has undergone cardiac surgery for bypass and has received retrograde cardioplegia.

 

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Table 2. pH, PO2, and PCO2 course during cross-clampinga

 
During each cardioplegic dose pH rose from an average of 7.24±0.10 to an average of 7.51±0.10. Maximal pH level was higher in retrograde cardioplegia (7.54±0.01) than in antegrade cardioplegia (7.43±0.04; P<0.001).

During every ischemic period pH decreased. The pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. Fast decline took place in 1.36±1.06 min, and accounted for a mean decrease of 32±16%, and a mean slope of -0.07±0.02 units per minute. Slow decline took place in 10.31±1.53 min, and accounted for remaining 68±16%, with a mean slope of -0.03±0.02 units per minute.

In subsequent cardioplegic doses, maximal pH reached comparable values with retrograde cardioplegia, but decreased with antegrade cardioplegia and in the third ischemic period it was significantly lower (7.39±0.09 vs. 7.54±0.06, P=0.01).

Lowest pH progressively decreased from 7.28±0.14 at the end of the first ischemic period to 7.18±0.19 at the end of the second (P=0.003), and to 7.16±0.19 at the end of the third (P=NS), with no differences between antegrade or retrograde cardioplegia.

3.2. Coronary sinus PO2
The typical time course of PO2 is reported in Fig. 4 . Relating data are reported in Table 2.



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Fig. 4. Tracing of the continuous monitoring of PO2 throughout the cross-clamping time as measured by the probe inserted in the coronary sinus. The value reached by PO2 at the end of each reperfusion phase was progressively reduced. Data from patients of Fig. 2.

 
During the first cardioplegic dose, PO2 rose to a maximum of 231±30 mmHg after retrograde perfusion and to 184±43 mmHg with antegrade perfusion (P=0.032).

After each cardioplegic dose, PO2 showed an initial rapid fall with a 90% decrease, at a rate of -33.5±9.1 mmHg per minute, within 5.00±1.23 min. The decrease was faster for antegrade than retrograde cardioplegia (2.41±0.07 min vs. 5.58±1.56 min, P<0.001). After the early fall, a plateau was seen at the mean slope of -1.0±0.3 mmHg per minute, without differences between antegrade and retrograde cardioplegia.

During subsequent cardioplegic doses, maximal PO2 decreased from 214±41 to 173±43 mmHg (P=0.002) in the second dose, and then stabilized (174±33 mmHg) in third dose. This behavior was mainly due to retrograde cardioplegia for which maximal PO2 decreased from 231±30 to 166±44 mmHg (P=0.01) in the second dose, and then stabilized (167±36 mmHg in third dose), while it remained stable with antegrade along subsequent cardioplegic doses (184±43 to 190±41 to 191±23 mmHg; P=NS).

3.3. Coronary sinus PCO2
PCO2 followed a typical pattern (Fig. 5 ) with a decrease during cardioplegia and a steady increase during ischemia. Relating data are reported in Table 2.



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Fig. 5. Tracing of the continuous monitoring of PCO2 throughout the cross-clamping time as measured by the probe inserted in the coronary sinus. PCO2 showed a steady rise at each interval, with incomplete normalization after subsequent reperfusions as demonstrated by the progressive increase of maximal value achieved before each reperfusion. Data from patients of Fig. 2.

 
Minimal PCO2 at the end of cardioplegia significantly increased from the first dose (23±8 mmHg) to the second (27±5 mmHg, P=0.02) and to the third (29±7 mmHg, P=0.05), and with no difference between antegrade and retrograde cardioplegia.

PCO2 increased at a mean rate of 1.60±0.15 mmHg per minute during clamping periods.

Maximal PCO2 at the end of ischemic period increased from the first cardioplegic dose (42±12 mmHg) to the second (47±7 mmHg, P=0.02) and to the third (53±23 mmHg, P=0.05), and with no difference between antegrade and retrograde cardioplegia.

3.4. Isolated blood
During the evaluating period of 18±3 min, in all tests isolated blood showed a slow, continuous decline in PO2 that did not exceed -15% of original level and slow, continuous increase in PCO2 that did not exceed +13% of the starting level. Finally, spontaneous changes of pH were characterized by a very slow continuous decline that did not exceed -5% of initial pH level. An example of spontaneous oxygen concentration reduction in the test syringe is reported in Fig. 5.


    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 
IWBC has proved to be a safe and effective technique for myocardial protection, and has been found to be as reliable as hypothermic blood cardioplegia [912]. IWBC is administered in a semi-schematic way, with an initial and several subsequent doses injected antegradely and/or retrogradely at intervals that have proved to be safe for ordinary surgery.

Attempts have been made to prolong ischemic intervals between subsequent doses of IWBC, this behavior being proved safe by postoperative evaluation of CPK, cardiac index, and need of inotropic support [13]. Anyway, in experiments on dogs, prolongation of ischemic periods up to 30 min has been associated with cardiac dysfunction as evaluated with phosphorus 31-magnetic resonance spectroscopy [14]. Moreover, a few papers report adverse effects of prolonged administration of IWBC [15] and some authors warn about the degree of metabolic acidosis in the myocardium [16].

At present, with IWBC no tools are available to judge the feasibility of prolonging ischemic intervals or to rapidly detect states of myocardial suffering due to malperfusion or increased oxygen consumption. Intra-operative evaluation of myocardial homeostasis during cardioplegia has been performed experimentally [17] but so far no protocol has evaluated the use of myocardial metabolites as a tool for monitoring adequacy of myocardial preservation [18].

Intra-myocardial pH has been studied extensively in the early 1980s when myocardial protection was based on cold crystalloid solutions [19,20]; its use in humans has been advocated [21,22] and described [19] but did not gain general use, being overcome by the handy myocardial temperature.

After the introduction of IWBC, few reports have appeared describing the evaluation of intra-operative myocardial acid–base status. Bical et al. [16] described the use of an intra-myocardial glass electrode for evaluating a series of patients operated under intermittent blood cardioplegia at normothermia and moderate hypothermia, and stated that IWBC was associated with more acidic conditions and less myocardial injury than cold intermittent antegrade blood cardioplegia during coronary surgery.

In this study, we investigated the feasibility of coronary sinus measurement of pH, PO2, and PCO2 as a continuous monitoring of myocardial protection during IWBC.

On the basis of our preliminary results, continuous gas monitoring of coronary sinus blood seems feasible throughout cross-clamping time and measurements of pH, PO2, and PCO2 in the coronary sinus during cardioplegic arrest are consistent with the repetitive alternations of myocardial ischemia and reperfusion.

Indeed, a typical pattern of blood gases changes was detected during cross-clamping.

During cardioplegia, pH increases with no difference between the antegrade and retrograde route and decreases during ischemic periods in a bi-phasic way. Indeed, typical pattern of pH during ischemia is characterized by an initial steep decline (possibly explained by re-distribution of cardioplegia) followed by a slower decrease, which is possibly an expression of true myocardial metabolic state. At subsequent doses of IWBC, pH fails to restore the previous levels, so that at the end of every subsequent ischemic period progressively lower levels of pH were recorded.

Oxygen tension rapidly increases during cardioplegia. The rise of PO2 is steep with retrograde cardioplegia, because of direct flow of oxygenated blood in coronary sinus, and slow with antegrade cardioplegia, due to wash-out of cardioplegia from myocardium. During ischemia, PO2 decays with an initial rapid fall at very low levels within few minutes. The pattern repeats at subsequent doses.

Carbon dioxide tension increases steadily during ischemic periods at a rate of 1.6 mmHg per minute. Subsequent doses of IWBC fail to restore the baseline PCO2 levels so that, at every following ischemic period, higher levels of carbon dioxide tension are detected.

These results cannot be explained as an expression of simple degradation of ‘pooling’ blood in the coronary sinus. Spontaneous deoxygenation and carboxylation of blood takes place at a much slower and continuous rate, with no aspects of rapid falls/flexus/plateau as observed in the study. Moreover, mixing of blood with the general circulation does not influence the observed change in oxygen, carbon dioxide and pH, as they took place both when the probe was loosely inserted into the coronary sinus via the right atrium, and when the coronary sinus ostium was directly cannulated.

Thus, it seems conceivable that the observed patterns reflect, directly and globally, the exchange of gases between myocardium and coronary vessels blood.

Our study indicates that, even in normal operational conditions, standard reperfusions may be inadequate in reversing ischemia, and an ‘ischemic debt’ may build up at every ischemia/reperfusion.

Although the clinical significance of the observed patterns needs validation on larger population and by means of specifically designed experiments, the described technique could be of great use for the following reasons.

Safety of prolonged operations could be warranted by preventing pH from showing progressive degradation, i.e. by prolonging late reperfusions or by shortening late ischemic periods.
Once a critical pH value is established, intra-operative pH monitoring could be of use in case of forced prolongation of the ischemic period.
The technique could be of interest in evaluating effects of different operative temperatures, different cardioplegic protocols, or different clinical presentations.


    5. Conclusions
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 
The present paper assesses the feasibility of blood pH, carbon dioxide, and oxygen tension monitoring of the coronary sinus blood, and demonstrates that these values modify sensibly throughout operations. These data suggest that myocardial oxygen ‘debt’, carbon dioxide accumulation, and myocardial acidosis take place throughout cross-clamping with IWBC. If findings of this work are confirmed by the study of longer cross-clamping times, it will be likely that specific behavior in myocardial protection could be required in case of complex cardiac operations.

Continuous gas monitoring of coronary sinus blood may represent a valid adjunct to perform adequate myocardial protection in these situations.


    Footnotes
 
Presented at the joint 15th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 9th Annual Meeting of the European Society of Thoracic Surgeons, Lisbon, Portugal, September 16–19, 2001.


    Appendix A. Conference discussion
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 
Mr D. Ngaage (Leeds, UK): How many doses of cardioplegia did you give these patients? And if you used retrograde cardioplegia through the coronary sinus, which, I suppose is where you were measuring your continuous metabolism, was it the same cannula that was used? And don't you think this would affect or influence your readings?

Thirdly, I wonder if the three parameters you measured will give an adequate reflection of myocardial metabolism, realizing that in the hypoxic situation that lactate and other triglycerides metabolites, could provide a good measure of myocardial metabolism.

Dr Graffigna: Probably I missed the third question, but in order to answer to the first one, the median cardioplegic doses were four doses, the beginning and three others, and in case of retrograde cardioplegia, we connected the injection of the cardioplegia to the (same) catheter carrying the pH probe (that was used for measuring pH).

Now, obviously this affects the maximal pH, not significantly, though, because the data showed that even with antegrade cardioplegia, the blood which reflows through the coronary sinus at some time will reach such a high level that it is the same (level that is) reached by retrograde cardioplegia. That means (So) we have performed a complete washout of the blood that was present in the heart during the previous ischemic time. (I don't know if I made myself understood.) If you perform antegrade cardioplegia, sooner or later you will flush (flood) all the blood out of the heart. This doesn't mean, though, (the fact) that (the blood reflowing from the coronary sinus in) antegrade cardioplegia is given for enough time to prevent CO2 accumulation and therefore decay of the pH throughout the cross-clamping time.(That is my opinion.)

So you may reach high levels of PO2 in the coronary sinus but not for a long enough time in order to completely ‘refuel’ (nourish) the myocardium, and therefore even (if) in standard procedures, with (which is) 3 min dose as induction (at the beginning), and 2 min subsequent doses (for each dose, I mean, we followed) according to the typical Calafiore protocol, pH slowly decays, and this, to my opinion, indicates that there is some degree (kind) of cardiac anoxia which is not reversed by each reperfusion (resituates at the end of each single ischemic time). Like scuba divers performing additional immersions (for a scuba diver, you know, when you perform subsequent immersions you) have to take care that the previous ones didn't leave residual (give you) nitrogen. (That is my belief. But I missed the third one.)

Mr Ngaage: Should you have measured more parameters besides the PO2, PCO2 and the pH?

Dr Graffigna: Yes. Actually, this probe is capable of performing only these (this) kinds of measurement, as it (You may calculate the bicarbs by calculation, but this probe) is devised only for intra-vascular measurement of pH, PO2, and PCO2. Actually our aim was only that of understanding if this item was capable of being used for monitoring the myocardial conditions (situation) during intermittent warm blood cardioplegia.

Mr S. Nashef (Cambridge, UK): I very much enjoyed your study and I think it is very thought-provoking and will hopefully give us really quite a lot of insight into what happens in between the doses of cardioplegia. As I understand it, all the measurements are on coronary sinus blood?

Dr Graffigna: Exactly.

Mr Nashef: Normally do you think there is enough blood in the coronary sinus at all times, and how well do you think this reflects the true state of the myocardium?

Dr Graffigna: I didn't say that this probe doesn't work by means of drawing blood from the coronary sinus. This works by contact, (because) as the sensor is sensible (sensitive) to the modification in the gel which surrounds (all) the probe(s), and therefore there is no need for drawing blood in the coronary sinuses.

Mr Nashef: No, I understood that. I am not talking about drawing blood, but there still has to be blood in the coronary sinus for the probe to measure, and if there is no flow down the coronaries there may not be any blood or there may be just a stagnant pool that is left over from before, which doesn't tell you much about the function of the myocardium. That was my point.

Dr Graffigna: We observed a ‘rhythmic’ decay in PO2, PCO2 and pH throughout the cross-clamping time. Now, we put (performed exactly the same thing by putting) oxygenated blood in a cup and measured (ing) the intrinsic consumption by means of the same probe. The consumption of PO2 throughout the time takes place at such a slow rate that it is nearly flat, so what we observed in the patients was typically an expression of an ischemic tissue and not the decay of pooled blood. (It doesn't decay – (gap in audio tape, please fill in) – that could be a concern, and we demonstrated that that was not true.)

Another concern was that of mixing of the coronary sinus blood with the systemic blood. (That is a concern.) But when we perform the retrograde cardioplegia, we put a purse string around the coronary sinus, and so the probe measures only (directly) the coronary sinus blood (over there). Now, the blood gases course in this setting was very similar to that observed with antegrade cardioplegia, where the probe was inserted in the coronary sinus via the right atrium, and this probably means that mixing of blood in the coronary sinus is negligible (and the behavior between the antegrade, which means probe through the atrium, and the retrograde, which means probe through the coronary sinus, was nearly the same).

Mr C. Satur (Stoke-On-Trent, UK): Just a brief question. Could you remind me, please, with the protocol that you are using, what is the electrolyte constitution of your cardioplegia, is it just potassium or do you also have added magnesium to it?

Dr Graffigna: (No, absolutely.) We use the blood oxygenated with potassium according to the Calafiore protocol, that's all.

Mr Satur: You don't have magnesium to add to the cardioplegia?

Dr Graffigna: No. We just add KCl (to the blood).

Mr Satur: Would it be worthwhile investigating the possibility of additional myocardial protection with the addition of magnesium?

Dr Graffigna: We are getting into (such) a complex issue. This probe costs roughly $500, so we needed to concentrate on very standard operational situations. Obviously this probe could be used for any kind of investigation regarding myocardial preservation. I think that comparing different kinds of cardioplegia could be interesting, but so far our aim is that of understanding if these parameters (this) can be used in clinical practice as indexes of myocardial preservation, especially for long cross-clamping times.

Dr R. de Vivie (Cologne, Germany): Perhaps it would be a good idea to make biopsies to give more information about the functional status.


    References
 Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A. Conference...
 References
 

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