- Email: [email protected]
Telemetric Recording of Intrapleural Pressure
Journal of Surgical Research 138, 10 –14 (2007) doi:10.1016/j.jss.2006.07.014
Association for Academic Surgery, 2006 Telemetric Recording of Intrapleural Pressure 1 Mathew D. Ednick, M.D.,* Murali Pagala,† John-Pierre Barakat,† Gustavol Nino,* Prashant Shah,† Joseph N. Cunningham, Jr.,† Mikhail Vaynblat,† and Mikhail Kazachkov*,2 *Department of Pediatrics, Maimonides Infants and Children’s Hospital, Brooklyn, New York; and †Department of Cardiothoracic Surgery, Maimonides Medical Center, Brooklyn, New York Submitted for publication December 20, 2005
this method to be helpful in understanding the pathophysiology of various breathing disorders. © 2007 Elsevier
Background. Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. Materials and methods. After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/ second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. Results. In six dogs, the total mean ⴞ SD negative IPP was ⴚ10.8 ⴞ 10.6 mmHg. After normalizing with respect to acquisition time it was ⴚ13.2 ⴞ 11.2 mmHg/ min. The actual inspiratory pressure was ⴚ19.7 ⴞ 15.3, and the expiratory pressure was ⴚ11.0 ⴞ 12.9. Conclusions. Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show
Inc. All rights reserved.
Key Words: intrapleural pressure; inspiratory pressure; expiratory pressure; telemetry; dog. INTRODUCTION
Intrapleural pressure (IPP) is the acting force within the pleural cavity that keeps the lungs constantly inflated. It is a product of the surface tension of alveolar fluid, compliance of lung tissue and the chest wall, and frictional resistance of airways [1]. Variations in these factors can have profound effects IPP measurements [2]. IPP is an important parameter in assessing many pathologic states. The disease processes that lead to increased resistance to airflow and increased inspiratory effort require greater negative pressures in the pleural space to maintain normal lung volumes [3]. Such changes in inspiratory IPP have been demonstrated in dogs with pulmonary edema and atelectasis [4, 5]. Alternatively, obstructive diseases such as asthma and COPD increase expiratory resistance, necessitating greater positive pleural pressures to generate adequate expiratory flow [3]. Previous investigators have used methods that recorded IPP in anesthetized dogs or obtained intraesophageal pressures as a substitute for IPP [6 –9]. Previously we have been studying the pathophyiological mechanisms of gastro-esophageal reflux and aspiration in a dog model [9 –11]. These studies necessitated long term monitoring of intrapleural pressure in conscious animals. We hypothesized that IPP can be measured in conscious animals over prolonged period of time using telemetry. In this study, we describe a telemetric method, which allows for the recording of IPP either intermittently or continuously in conscious, unanesthetized dogs.
1 Presented at the 1 st Annual Academic Surgical Congress (Association for Academic Surgery), San Diego, CA, February 7–11, 2006. 2 To whom correspondence and reprint requests should be addressed at Infants and Children’s Hospital of BrooklynPediatrics, Division of Pediatirc Pulmonology, 4802 10th Avenue, Brooklyn, NY 11219. E-mail: [email protected].
0022-4804/07 $32.00 © 2007 Elsevier Inc. All rights reserved.
10
EDNICK ET AL.: TELEMETRIC RECORDING OF INTRAPLEURAL PRESSURE
MATERIALS AND METHODS Animal Care This study, after approval from the Institutional Animal Care and Use Committee (IACUC), used six mongrel dogs. They were maintained in facilities that were in compliance with the Guide for the Care and Use of Laboratory Animals published by the National Institute of Health (NIH publication #85-23, revised 1996), under the supervision of a veterinarian.
Surgical Procedure The procedure for surgical implantation of the telemetric device was similar to that used by Vaynblat et al. [12]. Each dog was sedated with sodium pentobarbital 20 to 30 mg/kg and then anesthetized with sodium thiopental 10 to 20 mg/kg. After endotracheal intubation, 0.5% isoflurane was used to maintain anesthesia. A telemetric implant was positioned subcutaneously and secured with sutures in each dog. The tip of the pressure sensor catheter from the implant was inserted directly into the pleural space, and the catheter secured with 3-0 braided silk sutures. The surgical wound was then closed. Figure 1 shows the dog with the telemetric implant.
Telemetric Monitoring The telemetric implant used was model TL11M2-D70-PCT from Data Science International. The battery of the implant could be switched on and off using a magnet. The “on” position was identified when a high pitched sound on an FM radio was heard. The pressure signals were monitored through a RLA 2000 telemetric receiver, multiplexed with a Dataquest Acquisition Board housed in a computer. Starting from post-operative day 2, the pressure signals were recorded at a sampling rate of 100 points/second at 20 s intervals for 15 to 35 min daily for 4 days.
Signal Analysis Typical IPP signals (Fig. 2A) recorded from each dog were digitally averaged. The mean IPP values (mmHg) were plotted against the acquisition time (Fig. 2B). From this curve an amplitude histogram was plotted (Fig. 2C). Using only the negative amplitude ranges and their respective counts, a total mean negative IPP value
11
was calculated using the formula [(F*MR)/T], where F is the frequency count, MR is the midrange pressure value, and T is the total acquisition time. IPP values are expressed as total negative mean mmHg, and also as negative mean mmHg/30 min, after normalizing the value with respect to 30 min acquisition time for easy comparison between different dogs. Furthermore, using stable recordings from each dog, the mean inspiratory IPP and the mean expiratory IPP were also measured.
Statistical Analysis Descriptive statistics were obtained using SigmaStat software package. Values are expressed as mean ⫾ SD, and also median along with the 25th and 75th percentiles.
RESULTS
The total negative IPP had a mean (⫾SD) value of ⫺10.8 ⫾ 10.6 mmHg, and a median value of ⫺6.8, with the 25% and 75% percentile values of ⫺16.2 and ⫺3.3 mmHg (Table 1). When the total negative IPP values from each dog was normalized for 30 min acquisition time, the normalized negative IPP had a mean value of ⫺13.2 ⫾ 11.2 mmHg, with the median (25th, 75th percentiles) value of ⫺8.3 (⫺25.8, ⫺6.3) mmHg (Table 1). The normalized negative IPP value was close to the actual inspiratory IPP mean value of ⫺19.7 ⫾ 15.3 mmHg, and median value of ⫺15.2 (⫺24.6, ⫺9.1) mmHg (Table 1). The measured expiratory IPP had a mean value of ⫺11.0 ⫾ 12.9 mmHg, and a median of ⫺6.4 (⫺12.9, ⫺2.6) mmHg (Table 1). DISCUSSION
The present study showed that IPP can be accurately monitored using a telemetric method. The advantages of this method are (1) pressures can be recorded in
FIG. 1. The dog with subcutaneously placed telemetric implant disk. The tip of the pressure sensor catheter from the implant (ions tube below the lifted shoulder) was inserted into the pleural space. The plastic capsule of the implant is shown as an insert on the left bottom of the figure. (Color version of figure is available online.)
12
JOURNAL OF SURGICAL RESEARCH: VOL. 138, NO. 1, MARCH 2007
FIG. 2. Intrapleural pressure signals monitored telemetrically from a conscious dog. (A) Original pressure signals recorded for 20 sec. (B) Plot of the digitally averaged pressure signals recorded from the same dog over 22 min. (C) Histogram representing the amplitude distribution of the averaged pressure signals recorded over the duration of 22 min.
unanesthetized, awake dogs, (2) direct measurements of IPP are obtained, and (3) recording times can range from minutes to days.
IPP has been measured in dogs by previous investigators. These investigations found similar results to those obtained in the present study. Farhi et al. [6]
13
EDNICK ET AL.: TELEMETRIC RECORDING OF INTRAPLEURAL PRESSURE
TABLE 1 IPP Telemetrically Monitored from Six Conscious Dog# IPP
Record duration (min)
Mean IPP (mmHg)
Mean IPP/30 min (mmHg)
Inspiratory IPP (mmHg)
Expiratory (mmHg)
1 2 3 4 5 6
35 17 16 29 22 33
⫺30.0 ⫺16.2 ⫺3.3 ⫺6.4 ⫺7.2 ⫺1.9 ⫺10.8 ⫾ 10.6 ⫺6.8 (⫺16.2, ⫺3.3)
⫺25.8 ⫺28.5 ⫺6.3 ⫺6.6 ⫺9.9 ⫺1.8 ⫺13.2 ⫾ 11.2 ⫺8.3 (⫺25.8, ⫺6.3)
⫺18.0 ⫺24.6 ⫺6.3 ⫺16.7 ⫺13.6 ⫺9.1 ⫺19.7 ⫾ 15.3 ⫺15.2 (⫺24.6, ⫺9.1)
⫺36.0 ⫺12.9 ⫺1.9 ⫺8.7 ⫺4.0 ⫺2.6 ⫺11.0 ⫾ 12.9 ⫺6.4 (⫺12.9, ⫺2.6)
Mean ⫾ S.D. Median (25%, 75% Percentiles)
recorded IPP in multiple points of anesthetized dogs’ chests. Their recorded peak inspiratory IPPs ranged from ⫺7.0 cmH 2O to ⫺14.3 cmH 2O, the mean being ⫺9.34 cmH 2O (⫺6.87 mmHg). They also recorded end expiratory IPPs that were in the range of ⫺3.5 cmH 2O and ⫺6.8 cmH 2O, with a calculated mean of ⫺5.12 cmH 2O (⫺3.77 mmHg). Algren et al. [4] measured baseline IPP in dogs before inducing pulmonary edema. Results indicated pressures of approximately ⫺5 mmHg. The main limitation of the aforementioned studies was the fact that IPP was measured in unconscious, restrained animals. This prevented the investigators from performing the recordings over prolonged periods of time in the conscious animals. An additional study that recorded intrapleural pressures in dogs was done by Tosev et al. [13]. IPP was recorded in dogs using a surgically implanted device in the pleural space. The device was directly connected to the pressure transducer via a steel tubing. Pressures were measured at rest, at exercise, and at deep inspiration. The IPPs at rest varied between ⫺2 mmHg and ⫺8 mmHg. This method has several disadvantages. Although the dogs remained conscious, the presence of connecting tubing prevented them from their usual activities making them semi-restrained. Also, errors in IPP readings could be caused by compression of connecting tubing. Other studies relied upon indirect measurements of IPP from intraesophageal pressures. Some of these have shown that changes in esophageal pressures can accurately assess changes in pleural pressure [7, 14]. In our previous study the values of intraesophageal inspiratory pressures in anesthetized dogs were ⫺11.8 ⫾ 4.8 cm H 2O [9]. Rutishauser et al. [15] also measured intraesophageal pressures in dogs while they were supported in the supine and prone positions. The mean esophageal pressures from that study were ⫺1.3 ⫾ 0.61 cm H 2O and ⫺4.6 ⫾ 0.79 cm H 2O, respectively. Both of these studies do report pressures that are similar to the IPP values in the present study. However, esophageal pressure measurements can be unreliable and substantially different from pleural pressure during quiet breathing [16]. Stiffness of the esophagus
secondary to increased smooth muscle tone or weights of surrounding mediastinal structures are possible causes of this discrepancy [17]. There are just few reports on assessing the IPP in conscious animals [18 –20]. Dorato et al. [18] evaluated pulmonary mechanics in conscious rats over varying durations of time using a plethysmographic system and intraesophageal catheter to estimate pleural pressures. In addition to the limitations of intraesophageal catheters previously described, there are limitations of a plethysmographic system. Plethysmography often requires the animal to be restrained by an airtight seal around the neck or on occasion, by a facemask over the head. This can create an environment of high stress and anxiety for the animal being studied, and result in inaccurate pressure measurements [19]. Santing et al. [19] measured airway functions in unanesthetized, unrestrained guinea pigs using a specially designed pneumotachograph surgically implanted in the trachea. Use of a pneumotachograph within the trachea will decrease the airway diameter and inversely affect resistance. Pneumotachography also requires frequent calibration of the instruments being used [20]. We are aware of only one study that used a telemetric method for measurement of IPP similar to the present study. Murphy et al. used telemetry to measure pleural pressure in conscious rats [21]. However, the transmitter and catheter were placed in the subpleural space, which provided the continuous monitoring of intramediastinal rather than IPP. The surgical technique for implantation involved a complicated abdominal approach with the incision through the abdominal musculature, which could potentially affect the physiology of breathing. Our study demonstrates that IPP can be measured directly in conscious dogs over extended periods of time, and the values of IPP are similar to those obtained by previous investigators using different methodology. A limitation to our technique is that the IPP signal is disturbed by mechanical movements of the dog such as barking, panting, and scratching the cage during the period of telemetric monitoring. To suppress such artifacts we used digital filtering. Furthermore,
14
JOURNAL OF SURGICAL RESEARCH: VOL. 138, NO. 1, MARCH 2007
use of only the negative IPP values ensured physiologically relevant signal analysis. Despite these measures, there was considerable variation in the mean IPP values (Table 1). To rule out errors in analysis of mean IPP data, we directly measured the inspiratory and expiratory portions of the IPP signal from well defined stable recordings. The variability still persisted, especially in dogs 1 and 2 (Table 1). This may not be because of malfunction of the catheter resulting in dislodgement from the pleural cavity, because the catheter was firmly secured to the fascia and the intercostals muscles by surgical suture. Plugging of the catheter lumen would lead to an abnormally high steady baseline without biphasic signal. These considerations indicate that physiological factors such as anxiety and biological variations may also influence the IPP recordings, especially because these dogs were not anesthetized or restrained. In conclusion, our study provides a telemetric technique for intermittent or continuous recording of IPP in fully conscious, unrestrained dogs, which may provide important insight into IPP changes during the post-surgical period or in pathological conditions associated with various breathing disorders.
6.
7.
8.
9.
10.
11.
12.
13.
14.
ACKNOWLEDGMENTS
15.
This study was supported by a grant from the Maimonides Research and Development Foundation, and from the Department of Pediatrics.
16.
REFERENCES Lai-Fook SJ, Rodarte JR. Pleural pressure distribution and its relationship to lung volume and interstitial pressure. J Appl Physiol 1991;70:967. 2. Felekis VA. The contribution of intrapleural pressures to the pathogenesis of emphysema. Med Hypotheses 2005;64:298.
17.
1.
3.
Mergoni M, Rossi A. Physiopathology of acute respiratory failure in COPD and asthma. Minerva Anestesiol 2001;67:198.
4.
Algren JT, Price RD, Buchino JJ, Stremel RW. Pulmonary edema associated with upper airway obstruction in dogs. Pediatric Emergency Care 1993;9:332.
5.
Chen L, Williams JJ, Alexander CM, Ray RJ, Marshall C,
18.
19.
20. 21.
Marshall BE. The effect of pleural pressure on the hypoxic pulmonary vasoconstrictor response in closed chest dogs. Anesth Analg 1988;67:763. Farhi L, Otis AB, Proctor DF. Measurement of intrapleural pressure at different points in the chest of a dog. J Appl Physiol 1957;10:15. Gillespie DJ, Lai YL, Hyatt RE. Comparison of esophageal and pleural pressures in the anesthetized dog. J Appl Physiol 1973; 35:709. Sackner MA, Grenvik S, Moavero NE, et al. Pleural pressure changes in dogs measured from suprasternal fossa movements. J Appl Physiol 1990;68:1265. Boesch RP, Shah P, Vaynblat M, et al. Relationship between upper airway obstruction and gastroesophageal reflux in a dog model. J Invest Surg 2005;18:241. Savchenko O, Dhadwal AK, Pagala M, et al. Lipid-laden macrophage index in healthy canines. Eur J Clin Invest 2006;36: 419. Kazachkov M, Marcus M, Vaynblat M, Nino G, Pagala M. Correlation of intrapleural pressures with severity of gastroesophageal reflux in experimental model. Proceedings of ATS 2006;3:A822. Vaynblat M, Pagala MK, Davis WJ, et al. Telemetrically monitored arrhythmogenic effects of doxorubicin in a dog model of heart failure. Pathophysiology 2003;9:241. Tosev J, Daley L, Hilton A. A method for recording intrpleural pressure in conscious semi-restrained mammals. J Appl Physiol 1969;27:902. Koo Kw, Leith DE, Sherter CB, Snider GL. Respiratory mechanics in normal hamsters. J Appl Physiol 1976;40:936. Rutishauser W, Banchero N, Tsakiris A, Sturm R, Wood E. End-expiratory pleural pressures in dogs in supine and prone body positions studied without thoracotomy. AMRL-TR 1964; 94:1. Mead J, Gaensler E. Esophageal and pleural pressures in man, upright and supine. J Appl Physiol 1959;14:81. Baydur A, Behrakis PK, Zin WA, Jaeger M, Milic-Emili J. A simple method for assessing the validity of the esophageal balloon technique. Am Rev Respir Dis 1982;126:788. Dorato MA, Carlson KH, Copple DL. Pulmonary mechanics in conscious Fischer 344 rats: Multiple evaluations using nonsurgical techniques. Toxicol Appl Pharmacol 1983;68:344. Santing RE, Meurs H, van der Mark TW, et al. A novel method to assess airway function parameters in chronically instrumented, unrestrained guinea pigs. Pulm Pharmacol 1992;5:265. AARC-APT Clinical Practice Guidelines. Respiratory care 1995; 40:1336. Murphy DJ, Renninger JP, Gossett KA. A novel method for chronic measurement of pleural pressure in conscious rats. J Pharmacol Toxicol Methods 1998;39:137.
Association for Academic Surgery, 2006 Telemetric Recording of Intrapleural Pressure 1 Mathew D. Ednick, M.D.,* Murali Pagala,† John-Pierre Barakat,† Gustavol Nino,* Prashant Shah,† Joseph N. Cunningham, Jr.,† Mikhail Vaynblat,† and Mikhail Kazachkov*,2 *Department of Pediatrics, Maimonides Infants and Children’s Hospital, Brooklyn, New York; and †Department of Cardiothoracic Surgery, Maimonides Medical Center, Brooklyn, New York Submitted for publication December 20, 2005
this method to be helpful in understanding the pathophysiology of various breathing disorders. © 2007 Elsevier
Background. Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. Materials and methods. After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/ second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. Results. In six dogs, the total mean ⴞ SD negative IPP was ⴚ10.8 ⴞ 10.6 mmHg. After normalizing with respect to acquisition time it was ⴚ13.2 ⴞ 11.2 mmHg/ min. The actual inspiratory pressure was ⴚ19.7 ⴞ 15.3, and the expiratory pressure was ⴚ11.0 ⴞ 12.9. Conclusions. Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show
Inc. All rights reserved.
Key Words: intrapleural pressure; inspiratory pressure; expiratory pressure; telemetry; dog. INTRODUCTION
Intrapleural pressure (IPP) is the acting force within the pleural cavity that keeps the lungs constantly inflated. It is a product of the surface tension of alveolar fluid, compliance of lung tissue and the chest wall, and frictional resistance of airways [1]. Variations in these factors can have profound effects IPP measurements [2]. IPP is an important parameter in assessing many pathologic states. The disease processes that lead to increased resistance to airflow and increased inspiratory effort require greater negative pressures in the pleural space to maintain normal lung volumes [3]. Such changes in inspiratory IPP have been demonstrated in dogs with pulmonary edema and atelectasis [4, 5]. Alternatively, obstructive diseases such as asthma and COPD increase expiratory resistance, necessitating greater positive pleural pressures to generate adequate expiratory flow [3]. Previous investigators have used methods that recorded IPP in anesthetized dogs or obtained intraesophageal pressures as a substitute for IPP [6 –9]. Previously we have been studying the pathophyiological mechanisms of gastro-esophageal reflux and aspiration in a dog model [9 –11]. These studies necessitated long term monitoring of intrapleural pressure in conscious animals. We hypothesized that IPP can be measured in conscious animals over prolonged period of time using telemetry. In this study, we describe a telemetric method, which allows for the recording of IPP either intermittently or continuously in conscious, unanesthetized dogs.
1 Presented at the 1 st Annual Academic Surgical Congress (Association for Academic Surgery), San Diego, CA, February 7–11, 2006. 2 To whom correspondence and reprint requests should be addressed at Infants and Children’s Hospital of BrooklynPediatrics, Division of Pediatirc Pulmonology, 4802 10th Avenue, Brooklyn, NY 11219. E-mail: [email protected].
0022-4804/07 $32.00 © 2007 Elsevier Inc. All rights reserved.
10
EDNICK ET AL.: TELEMETRIC RECORDING OF INTRAPLEURAL PRESSURE
MATERIALS AND METHODS Animal Care This study, after approval from the Institutional Animal Care and Use Committee (IACUC), used six mongrel dogs. They were maintained in facilities that were in compliance with the Guide for the Care and Use of Laboratory Animals published by the National Institute of Health (NIH publication #85-23, revised 1996), under the supervision of a veterinarian.
Surgical Procedure The procedure for surgical implantation of the telemetric device was similar to that used by Vaynblat et al. [12]. Each dog was sedated with sodium pentobarbital 20 to 30 mg/kg and then anesthetized with sodium thiopental 10 to 20 mg/kg. After endotracheal intubation, 0.5% isoflurane was used to maintain anesthesia. A telemetric implant was positioned subcutaneously and secured with sutures in each dog. The tip of the pressure sensor catheter from the implant was inserted directly into the pleural space, and the catheter secured with 3-0 braided silk sutures. The surgical wound was then closed. Figure 1 shows the dog with the telemetric implant.
Telemetric Monitoring The telemetric implant used was model TL11M2-D70-PCT from Data Science International. The battery of the implant could be switched on and off using a magnet. The “on” position was identified when a high pitched sound on an FM radio was heard. The pressure signals were monitored through a RLA 2000 telemetric receiver, multiplexed with a Dataquest Acquisition Board housed in a computer. Starting from post-operative day 2, the pressure signals were recorded at a sampling rate of 100 points/second at 20 s intervals for 15 to 35 min daily for 4 days.
Signal Analysis Typical IPP signals (Fig. 2A) recorded from each dog were digitally averaged. The mean IPP values (mmHg) were plotted against the acquisition time (Fig. 2B). From this curve an amplitude histogram was plotted (Fig. 2C). Using only the negative amplitude ranges and their respective counts, a total mean negative IPP value
11
was calculated using the formula [(F*MR)/T], where F is the frequency count, MR is the midrange pressure value, and T is the total acquisition time. IPP values are expressed as total negative mean mmHg, and also as negative mean mmHg/30 min, after normalizing the value with respect to 30 min acquisition time for easy comparison between different dogs. Furthermore, using stable recordings from each dog, the mean inspiratory IPP and the mean expiratory IPP were also measured.
Statistical Analysis Descriptive statistics were obtained using SigmaStat software package. Values are expressed as mean ⫾ SD, and also median along with the 25th and 75th percentiles.
RESULTS
The total negative IPP had a mean (⫾SD) value of ⫺10.8 ⫾ 10.6 mmHg, and a median value of ⫺6.8, with the 25% and 75% percentile values of ⫺16.2 and ⫺3.3 mmHg (Table 1). When the total negative IPP values from each dog was normalized for 30 min acquisition time, the normalized negative IPP had a mean value of ⫺13.2 ⫾ 11.2 mmHg, with the median (25th, 75th percentiles) value of ⫺8.3 (⫺25.8, ⫺6.3) mmHg (Table 1). The normalized negative IPP value was close to the actual inspiratory IPP mean value of ⫺19.7 ⫾ 15.3 mmHg, and median value of ⫺15.2 (⫺24.6, ⫺9.1) mmHg (Table 1). The measured expiratory IPP had a mean value of ⫺11.0 ⫾ 12.9 mmHg, and a median of ⫺6.4 (⫺12.9, ⫺2.6) mmHg (Table 1). DISCUSSION
The present study showed that IPP can be accurately monitored using a telemetric method. The advantages of this method are (1) pressures can be recorded in
FIG. 1. The dog with subcutaneously placed telemetric implant disk. The tip of the pressure sensor catheter from the implant (ions tube below the lifted shoulder) was inserted into the pleural space. The plastic capsule of the implant is shown as an insert on the left bottom of the figure. (Color version of figure is available online.)
12
JOURNAL OF SURGICAL RESEARCH: VOL. 138, NO. 1, MARCH 2007
FIG. 2. Intrapleural pressure signals monitored telemetrically from a conscious dog. (A) Original pressure signals recorded for 20 sec. (B) Plot of the digitally averaged pressure signals recorded from the same dog over 22 min. (C) Histogram representing the amplitude distribution of the averaged pressure signals recorded over the duration of 22 min.
unanesthetized, awake dogs, (2) direct measurements of IPP are obtained, and (3) recording times can range from minutes to days.
IPP has been measured in dogs by previous investigators. These investigations found similar results to those obtained in the present study. Farhi et al. [6]
13
EDNICK ET AL.: TELEMETRIC RECORDING OF INTRAPLEURAL PRESSURE
TABLE 1 IPP Telemetrically Monitored from Six Conscious Dog# IPP
Record duration (min)
Mean IPP (mmHg)
Mean IPP/30 min (mmHg)
Inspiratory IPP (mmHg)
Expiratory (mmHg)
1 2 3 4 5 6
35 17 16 29 22 33
⫺30.0 ⫺16.2 ⫺3.3 ⫺6.4 ⫺7.2 ⫺1.9 ⫺10.8 ⫾ 10.6 ⫺6.8 (⫺16.2, ⫺3.3)
⫺25.8 ⫺28.5 ⫺6.3 ⫺6.6 ⫺9.9 ⫺1.8 ⫺13.2 ⫾ 11.2 ⫺8.3 (⫺25.8, ⫺6.3)
⫺18.0 ⫺24.6 ⫺6.3 ⫺16.7 ⫺13.6 ⫺9.1 ⫺19.7 ⫾ 15.3 ⫺15.2 (⫺24.6, ⫺9.1)
⫺36.0 ⫺12.9 ⫺1.9 ⫺8.7 ⫺4.0 ⫺2.6 ⫺11.0 ⫾ 12.9 ⫺6.4 (⫺12.9, ⫺2.6)
Mean ⫾ S.D. Median (25%, 75% Percentiles)
recorded IPP in multiple points of anesthetized dogs’ chests. Their recorded peak inspiratory IPPs ranged from ⫺7.0 cmH 2O to ⫺14.3 cmH 2O, the mean being ⫺9.34 cmH 2O (⫺6.87 mmHg). They also recorded end expiratory IPPs that were in the range of ⫺3.5 cmH 2O and ⫺6.8 cmH 2O, with a calculated mean of ⫺5.12 cmH 2O (⫺3.77 mmHg). Algren et al. [4] measured baseline IPP in dogs before inducing pulmonary edema. Results indicated pressures of approximately ⫺5 mmHg. The main limitation of the aforementioned studies was the fact that IPP was measured in unconscious, restrained animals. This prevented the investigators from performing the recordings over prolonged periods of time in the conscious animals. An additional study that recorded intrapleural pressures in dogs was done by Tosev et al. [13]. IPP was recorded in dogs using a surgically implanted device in the pleural space. The device was directly connected to the pressure transducer via a steel tubing. Pressures were measured at rest, at exercise, and at deep inspiration. The IPPs at rest varied between ⫺2 mmHg and ⫺8 mmHg. This method has several disadvantages. Although the dogs remained conscious, the presence of connecting tubing prevented them from their usual activities making them semi-restrained. Also, errors in IPP readings could be caused by compression of connecting tubing. Other studies relied upon indirect measurements of IPP from intraesophageal pressures. Some of these have shown that changes in esophageal pressures can accurately assess changes in pleural pressure [7, 14]. In our previous study the values of intraesophageal inspiratory pressures in anesthetized dogs were ⫺11.8 ⫾ 4.8 cm H 2O [9]. Rutishauser et al. [15] also measured intraesophageal pressures in dogs while they were supported in the supine and prone positions. The mean esophageal pressures from that study were ⫺1.3 ⫾ 0.61 cm H 2O and ⫺4.6 ⫾ 0.79 cm H 2O, respectively. Both of these studies do report pressures that are similar to the IPP values in the present study. However, esophageal pressure measurements can be unreliable and substantially different from pleural pressure during quiet breathing [16]. Stiffness of the esophagus
secondary to increased smooth muscle tone or weights of surrounding mediastinal structures are possible causes of this discrepancy [17]. There are just few reports on assessing the IPP in conscious animals [18 –20]. Dorato et al. [18] evaluated pulmonary mechanics in conscious rats over varying durations of time using a plethysmographic system and intraesophageal catheter to estimate pleural pressures. In addition to the limitations of intraesophageal catheters previously described, there are limitations of a plethysmographic system. Plethysmography often requires the animal to be restrained by an airtight seal around the neck or on occasion, by a facemask over the head. This can create an environment of high stress and anxiety for the animal being studied, and result in inaccurate pressure measurements [19]. Santing et al. [19] measured airway functions in unanesthetized, unrestrained guinea pigs using a specially designed pneumotachograph surgically implanted in the trachea. Use of a pneumotachograph within the trachea will decrease the airway diameter and inversely affect resistance. Pneumotachography also requires frequent calibration of the instruments being used [20]. We are aware of only one study that used a telemetric method for measurement of IPP similar to the present study. Murphy et al. used telemetry to measure pleural pressure in conscious rats [21]. However, the transmitter and catheter were placed in the subpleural space, which provided the continuous monitoring of intramediastinal rather than IPP. The surgical technique for implantation involved a complicated abdominal approach with the incision through the abdominal musculature, which could potentially affect the physiology of breathing. Our study demonstrates that IPP can be measured directly in conscious dogs over extended periods of time, and the values of IPP are similar to those obtained by previous investigators using different methodology. A limitation to our technique is that the IPP signal is disturbed by mechanical movements of the dog such as barking, panting, and scratching the cage during the period of telemetric monitoring. To suppress such artifacts we used digital filtering. Furthermore,
14
JOURNAL OF SURGICAL RESEARCH: VOL. 138, NO. 1, MARCH 2007
use of only the negative IPP values ensured physiologically relevant signal analysis. Despite these measures, there was considerable variation in the mean IPP values (Table 1). To rule out errors in analysis of mean IPP data, we directly measured the inspiratory and expiratory portions of the IPP signal from well defined stable recordings. The variability still persisted, especially in dogs 1 and 2 (Table 1). This may not be because of malfunction of the catheter resulting in dislodgement from the pleural cavity, because the catheter was firmly secured to the fascia and the intercostals muscles by surgical suture. Plugging of the catheter lumen would lead to an abnormally high steady baseline without biphasic signal. These considerations indicate that physiological factors such as anxiety and biological variations may also influence the IPP recordings, especially because these dogs were not anesthetized or restrained. In conclusion, our study provides a telemetric technique for intermittent or continuous recording of IPP in fully conscious, unrestrained dogs, which may provide important insight into IPP changes during the post-surgical period or in pathological conditions associated with various breathing disorders.
6.
7.
8.
9.
10.
11.
12.
13.
14.
ACKNOWLEDGMENTS
15.
This study was supported by a grant from the Maimonides Research and Development Foundation, and from the Department of Pediatrics.
16.
REFERENCES Lai-Fook SJ, Rodarte JR. Pleural pressure distribution and its relationship to lung volume and interstitial pressure. J Appl Physiol 1991;70:967. 2. Felekis VA. The contribution of intrapleural pressures to the pathogenesis of emphysema. Med Hypotheses 2005;64:298.
17.
1.
3.
Mergoni M, Rossi A. Physiopathology of acute respiratory failure in COPD and asthma. Minerva Anestesiol 2001;67:198.
4.
Algren JT, Price RD, Buchino JJ, Stremel RW. Pulmonary edema associated with upper airway obstruction in dogs. Pediatric Emergency Care 1993;9:332.
5.
Chen L, Williams JJ, Alexander CM, Ray RJ, Marshall C,
18.
19.
20. 21.
Marshall BE. The effect of pleural pressure on the hypoxic pulmonary vasoconstrictor response in closed chest dogs. Anesth Analg 1988;67:763. Farhi L, Otis AB, Proctor DF. Measurement of intrapleural pressure at different points in the chest of a dog. J Appl Physiol 1957;10:15. Gillespie DJ, Lai YL, Hyatt RE. Comparison of esophageal and pleural pressures in the anesthetized dog. J Appl Physiol 1973; 35:709. Sackner MA, Grenvik S, Moavero NE, et al. Pleural pressure changes in dogs measured from suprasternal fossa movements. J Appl Physiol 1990;68:1265. Boesch RP, Shah P, Vaynblat M, et al. Relationship between upper airway obstruction and gastroesophageal reflux in a dog model. J Invest Surg 2005;18:241. Savchenko O, Dhadwal AK, Pagala M, et al. Lipid-laden macrophage index in healthy canines. Eur J Clin Invest 2006;36: 419. Kazachkov M, Marcus M, Vaynblat M, Nino G, Pagala M. Correlation of intrapleural pressures with severity of gastroesophageal reflux in experimental model. Proceedings of ATS 2006;3:A822. Vaynblat M, Pagala MK, Davis WJ, et al. Telemetrically monitored arrhythmogenic effects of doxorubicin in a dog model of heart failure. Pathophysiology 2003;9:241. Tosev J, Daley L, Hilton A. A method for recording intrpleural pressure in conscious semi-restrained mammals. J Appl Physiol 1969;27:902. Koo Kw, Leith DE, Sherter CB, Snider GL. Respiratory mechanics in normal hamsters. J Appl Physiol 1976;40:936. Rutishauser W, Banchero N, Tsakiris A, Sturm R, Wood E. End-expiratory pleural pressures in dogs in supine and prone body positions studied without thoracotomy. AMRL-TR 1964; 94:1. Mead J, Gaensler E. Esophageal and pleural pressures in man, upright and supine. J Appl Physiol 1959;14:81. Baydur A, Behrakis PK, Zin WA, Jaeger M, Milic-Emili J. A simple method for assessing the validity of the esophageal balloon technique. Am Rev Respir Dis 1982;126:788. Dorato MA, Carlson KH, Copple DL. Pulmonary mechanics in conscious Fischer 344 rats: Multiple evaluations using nonsurgical techniques. Toxicol Appl Pharmacol 1983;68:344. Santing RE, Meurs H, van der Mark TW, et al. A novel method to assess airway function parameters in chronically instrumented, unrestrained guinea pigs. Pulm Pharmacol 1992;5:265. AARC-APT Clinical Practice Guidelines. Respiratory care 1995; 40:1336. Murphy DJ, Renninger JP, Gossett KA. A novel method for chronic measurement of pleural pressure in conscious rats. J Pharmacol Toxicol Methods 1998;39:137.