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Anesth Analg 2007; 105:1379-1384
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000282835.10607.b8
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CRITICAL CARE AND TRAUMA

The Effects of Different Dobutamine Infusion Rates on Hypercapnic Depression of Diaphragmatic Contractility in Pentobarbital-Anesthetized Dogs

Yoshitaka Fujii, MD, and Aki Uemura, MD

From the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan.

Address correspondence and reprint requests to Yoshitaka Fujii, MD, First Department of Anesthesiology, Toho University School of Medicine, 6-11-1 Ohmori-Nishi, Ohta-ku, Tokyo 143-8541, Japan. Address e-mail to yfujii{at}med.toho-u.ac.jp.


   Abstract
Top
 Abstract
Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
BACKGROUND: Previously, we demonstrated that dobutamine was more effective than dopamine for the improvement of diaphragmatic contractility during hypercapnia. Here, we studied the effects of different dobutamine infusion rates on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs.

METHODS: Animals were divided into four groups of six each. In each group, hypercapnia (80–90 mm Hg) was produced by adding 10% CO2 to inspired gas. When hypercapnia was established, group Dob 0 received no study drug; group Dob 5 was induced with dobutamine 5 µg · kg–1 · min–1; group Dob 10 was induced with dobutamine 10 µg · kg–1 · min–1; group Dob 15 was induced with dobutamine 15 µg · kg–1 · min–1. Study drugs were administered IV for 60 min. Diaphragmatic contractility was assessed by measurement of transdiaphragmatic pressure (Pdi).

RESULTS: In the presence of hypercapnia, in each group, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation decreased from baseline (P < 0.05). In group Dob 0, Pdi to each stimulus did not change from hypercapnia-induced values. In groups Dob 5, Dob 10 and Dob 15, during the study drug administration, Pdi at both stimuli increased from hypercapnia-induced values (P < 0.05). There was a significant positive correlation between dobutamine infusion rates and Pdi at both stimuli (P = 0.0001).

CONCLUSION: Dobutamine effectively improves hypercapnic depression of diaphragmatic contractility in an infusion rate-dependent manner in pentobarbital-anesthetized dogs.


   Introduction
Top
 Abstract
 Introduction
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Patients with chronic airway obstruction who are hypercapnic experience limited performance of respiratory muscles, especially the diaphragm (1,2). In normal human subjects, hypercapnia is associated with diaphragm muscle dysfunction causing a reduction of diaphragmatic force generated for a constant elective myographic activity (3). Several drugs have been evaluated for their effects on diaphragmatic contractility during hypercapnia (4). Aminophylline and neostigmine are effective for improving hypercapnic depression of diaphragmatic contractility, but isoproterenol does not affect diaphragm muscle dysfunction induced by hypercapnia (4). Previously, we compared the effects of dopamine 10 µg · kg–1 · min–1 and dobutamine 10 µg · kg–1 · min–1 on hypercapnic depression of diaphragmatic contractility in dogs, and concluded that dobutamine was more effective than dopamine for improving diaphragmatic contractility during hypercapnia (5). However, no published data are available for the relationship between dobutamine infusion rate and diaphragmatic contractility during hypercapnia. We therefore studied the effects of different dobutamine infusion rates on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs.


   METHODS
Top
 Abstract
 Introduction
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Institutional approval for the study was obtained from the animal care and use committee of the University of Tsukuba. Twenty-four healthy adult mongrel dogs, 16 males and 8 females, weighing 10–15 kg (12.6 ± 1.9 kg, mean ± sd), were anesthetized with pentobarbital (25 mg/kg initial dose + 2 mg · kg–1 · h–1 maintenance dose) IV to abolish spontaneous breathing and movement. This dose used in this experiment did not affect diaphragmatic contractility in dogs (6). To maintain the integrity of our results, no animals received preanesthetic medication and analgesics, which was in accordance with our previous studies (5,7,8). No muscle relaxants were used. Each dog underwent tracheal intubation, and oxygenation of arterial blood was controlled with a mixture of oxygen and air (fraction of inspired oxygen 0.4) to maintain Pao2 >100 mm Hg. Tidal volume was set to 15 mL/kg and ventilatory frequency was adjusted to 10–15 bpm to keep Paco2 35–40 mm Hg and pHa 7.35–7.45. Thus, volume-targeted ventilation without positive end-expiratory pressure was performed, and these settings were not changed throughout the experiment. The right femoral artery for monitoring arterial blood pressure and the right femoral vein for administering maintenance fluids (lactated Ringer's solution 10 mg · kg–1 · h–1) and pentobarbital were cannulated. Femoral arterial blood pressure was measured from the catheter placed on the femoral artery, which was connected to a pressure transducer and was calibrated to open atmosphere. The left femoral vein was cannulated for the study drug administration. Rectal temperature was monitored continuously and maintained at 36.5°C–37.5°C using a heating pad.

An esophageal balloon catheter (PE-200; Nion Koden, Tokyo, Japan) was placed in the lower one-third of the esophagus. A similar balloon catheter was placed in the stomach. Transdiaphragmatic pressure (Pdi), defined as gastric pressure minus esophageal pressure, was measured by connecting the proximal ends of these two balloon catheters to each side of a differential pressure transducer (TP-604; Nohon Koden) and an amplifier (Type 1257; Nihondenki San-ei, Tokyo, Japan). One balloon catheter was open to atmosphere, and the position of the other one was changed to obtain appropriate pressure. The position of balloons in the esophagus and the stomach was then confirmed. This measurement and calibration of Pdi was the same as in our previous experiments (5,7,8).

Both phrenic nerves were exposed at the neck and the stimulating electrodes were placed around them. Supramaximal electrical test stimuli of 0.1 ms duration were applied for 2 s at frequencies of 20 and 100 Hz with an electrical stimulator (SEN-3301; Nihon Kohden). Diaphragmatic contractility was evaluated by measuring the maximal Pdi generated by test stimuli after airway occlusion at functional residual capacity. Thus, during stimulations, mechanical ventilation was halted and the airways were occluded at end-expiration, to avoid changes in lung volume during diaphragmatic contractions. End-expiratory diaphragmatic geometry and muscle fiber length during contractions were kept constant by placing a close-fitting plaster cast around the abdomen and lower one-third of the rib cage throughout the experiment.

The electrical activity of the crural and costal parts of the diaphragm (Edi-cru and Edi-cost, respectively) were recorded with two pairs of fishhook electrodes placed through a midline laparotomy; the electrodes were positioned in the anterior portion of the crural part near the central tendon and the anterior portion of the costal part in the right hemidiaphragm. The abdomen was then sutured.

The signal was rectified and integrated with an integrator (Type 1322; Nihondenki San-ei) with a time constant of 0.1 s and was regarded as Edi-cru and Edi-cost. Typical records of Pdi, Edi-cru, and Edi-cost at 20 and 100 Hz stimulation are shown in Figure 1. Using a differential pressure transducer, we could not obtain any waveforms of gastric pressure and esophageal pressure in this experiment. Two stimulations were performed at 20 and 100 Hz, and the average value of the 2 was used in the data analysis.


Figure 133
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  		Figure 1. Typical records of Pdi, Edi-cru, and Edi-cost at 20- and 100-Hz stimulation. Pdi = transdiaphragmatic pressure; Edi-cru = integrated electrical activity of the crural part of diaphragm; Edi-cost = integrated electrical activity of the costal part of diaphragm.

 

Dogs were allowed to stabilize for 30 min before study initiation after animal preparation. They were randomly divided into four groups of six each. In each group, baseline measurements of heart rate (HR), mean arterial blood pressure (MAP), arterial blood gas tensions (pHa, Paco2, Pao2), Pdi, Edi-cru, and Edi-cost were recorded. Hypercapnia (Paco2 80–90 mm Hg) was produced by adding 10% CO2 to the inspired gas. When hypercapnia was established at 2 h after the onset of CO2 administration, group Dob 0 received no study drug, group Dob 5 was induced with dobutamine 5 µg · kg–1 · min–1, group Dob 10 was induced with dobutamine 10 µg · kg–1 · min–1, and group Dob 15 was induced with dobutamine 15 µg · kg–1 · min–1. The study drug was continuously administered IV for 60 min with an infusion pump. Immediately after the cessation of dobutamine administration, HR, MAP, arterial blood gas tensions, Pdi, Edi-cru, and Edi-cost were measured. After the experiment was finished, animals were killed with an overdose of pentobarbital.

Before beginning the study, we conducted a power analysis, which indicated that six dogs in each group would be required to detect a difference in Pdi to each stimulus among baseline, hypercapnia, and treatment periods with a power (1-ß) of 0.8 ({alpha} = 0.05). Values are mean ± sd. Statistical analysis was performed using ANOVA for repeated measurements, followed by the Bonferroni/Dunn test for multiple comparisons and Student's t-test, as appropriate. Regression analysis was used to assess the relationship between dobutamine dose and Pdi at both stimuli. P < 0.05 was considered significant.


   RESULTS
Top
 Abstract
 Introduction
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
No differences in HR, MAP, arterial blood gas tensions, Pdi, Edi-cru, and Edi-cost during baseline were observed among the groups. When hypercapnia was established, HR and MAP increased from baseline in each group (P < 0.05). With an infusion of dobutamine (groups Dob 5, Dob 10, and Dob 15), HR and MAP increased from values obtained during hypercapnia (P < 0.05). Administration of CO2 led to an increase in Paco2 (P < 0.05) and a decrease in pHa (P < 0.05) in each group. No difference in Pao2 was found throughout the experiment (Table 1). No cardiac dysrhythmias were observed in any of the groups.


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  		Table 1. Hemodynamics and Arterial Blood Gas Tensions

 

In the presence of hypercapnia, Pdi at both stimuli decreased from baseline in each group (P < 0.05). In group Dob 0, Pdi to each stimulus did not change from hypercapnia-induced values. In groups Dob 5, Dob 10, and Dob 15, during the study drug administration, Pdi at both stimuli increased from hypercapnia-induced values (P < 0.05). No changes in %Edi-cru and %Edi-cost were observed throughout the experiment in any group (Table 2).


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  		Table 2. Pdi and %Edi

 

There was a positive correlation between dobutamine infusion rates and Pdi at both stimuli (Fig. 2). The regression equations were: Pdi at 20 Hz stimulation (cm H2O) = 0.57 x dobutamine dose (µg · kg–1 · min–1) + 12.76 (P = 0.0001) and Pdi at 100 Hz stimulation = 0.73 x dobutamine dose (µg · kg–1 · min–1) + 18.60 (P = 0.0001).


Figure 233
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  		Figure 2. Relationship between dobutamine infusion rates and Pdi at 20 and 100-Hz stimulation. Pdi = transdiaphragmatic pressure. There was a positive correlation between dobutamine infusion rates and Pdi at both stimuli. The regression equations were Pdi at 20-Hz stimulation (cm H2O) = 0.57 x dobutamine dose (µg · kg–1 · min–1) + 12.76 (P = 0.0001) and Pdi at 100-Hz stimulation = 0.73 x dobutamine dose (µg · kg–1 · min–1) + 18.60 (P = 0.0001).

 


   DISCUSSION
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The main findings of this study were as follows: when hypercapnia (80–90 mm Hg) was established, Pdi at 20 and 100 Hz stimulation decreased from baseline (P < 0.05); with an infusion of dobutamine (5–15 µg · kg–1 · min–1), Pdi at both stimuli increased from hypercapnia-induced values (P < 0.05); there was a significant positive correlation between dobutamine infusion rates and Pdi at both stimuli (P = 0.0001).

Diaphragmatic contractility is assessed by force-frequency characteristics (9,10), and is often evaluated by the measurement of Pdi, which is affected by the length and geometry of the diaphragm in a precontracted condition (11). A major determinant of diaphragmatic length and geometry is lung volume. Conceivably, the change in Pdi may be secondary to changes in end-expiratory lung volume. In this experiment, the airway was occluded at the end-expiratory lung volume (i.e., functional residual capacity) during measurements. To avoid the deformation of thoracoabdominal structures, the plaster cast around the abdomen was also placed on the lower one-third of the rib cage. Thus, constancy of diaphragmatic geometry and muscle length during contractions was achieved (6).

Hypercapnia impairs diaphragmatic contractility in vivo (12) and in vitro (13). Yanos et al. (12) estimated diaphragmatic performance from the change in Pdi after supramaximal stimulation of the phrenic nerves in open-chested, casted-abdomen dogs during hypercapnia (Paco2 79 mm Hg), and found an 18% decrease in Pdi compared with baseline. Similarly, in the in vitro rat diaphragm, the force of contractions in animals exposed to hypercapnic conditions (Pco2 191 mm Hg) was less than in animals exposed to normocapnic conditions (13).

In this study, we demonstrated that Pdi at 20 and 100 Hz stimulation decreased by 15% from baseline (all P < 0.05) in the presence of hypercapnia (Paco2 80–90 mm Hg). This was in agreement with a previous report showing that development of hypercapnia (Paco2 87 mm Hg) produces a 10% reduction in Pdi at low and high frequencies of stimulation (4). The mechanism by which hypercapnia reduces diaphragmatic contractility is unknown. However, there is a possibility that an alteration of muscle pH may be related to a decrease in the affinity of troponin for calcium, an increase in the binding of calcium by the sarcoplasmic reticulum, or a reduction of the rate of glycolysis and thus adenosine triphosphate resynthesis (14–16). The selective loss of force at 20-Hz stimulation is closely related to the impairment of excitation– contraction coupling (17), and the selective loss of force and electromyographic activity at 100-Hz stimulation suggests neuromuscular transmission failure (18,19). Therefore, the decrease in Pdi at both stimuli (without a reduction of Edi at 100-Hz stimulation) observed during hypercapnia is presumably due to the impairment of excitation–contraction coupling, and, in part, to neuromuscular transmission failure in the canine diaphragm.

In the present study, we demonstrated that Pdi at 20 and 100 Hz stimulation significantly increased from hypercapnia-induced values with an infusion of dobutamine (5–15 µg · kg–1 · min–1). Also, there was a significant correlation between dobutamine infusion rates and Pdi at both stimuli. Therefore, it is suggested that dobutamine increases reduced diaphragmatic contractility produced by hypercapnia in an infusion rate-dependent manner.

The exact mechanism by which dobutamine enhances diaphragmatic contractility during hypercapnia remains unclear. However, it has been suggested that dobutamine may have a direct positive effect on contractility of the diaphragm (20). Previously, we found complete blocking of the dobutamine-enhancing action with nicardipine calcium channel blockade, in the diaphragm. This effect of dobutamine is believed to be the result of cyclic AMP-induced alterations in the rate of calcium ion uptake by the sacroplasmic reticulum (20). Howell et al. (4) investigated the effects of aminophylline, isoproterenol, and neostigmine on decreased diaphragmatic contractility induced by hypercapnia, and concluded that aminophylline and neostigmine, but not isoproterenol, improved diaphragmatic contractility during hypercapnia. Our results suggest that dobutamine, as well as aminophylline and neostigmine, improves hypercapnic depression of diaphragmatic contractility by virtue of its enhancing effect.

Diaphragmatic contractility depends on the energy supply to the diaphragm, which is related to the blood supply to the diaphragm, and cardiac output (CO) is one of the major factors for determining blood flow to the diaphragm (21). In this experiment, we did not measure CO as well as diaphragmatic blood flow during dobutamine administration. However, in a previous report, we observed that CO increased with an infusion of combined dobutamine and nicardipine without augmentation of diaphragmatic contractility, and postulated that the effect of dobutamine on diaphragmatic contractility was not due to changes in blood flow to the diaphragm.

Signs of CO2 retention are tachycardia and hypertension (22). When hypercapnia (Paco2 80–90 mm Hg) was established in the present study, we found significant increases in HR and MAP compared with baseline. During dobutamine administration (groups Dob 5, Dob 10, and Dob 15), HR and MAP significantly increased from hypercapnia-induced values. Rapid infusion rates of dobutamine (>10 µg · kg–1 · min–1) occasionally cause cardiac dysrhythmias (23). However, in this experiment, no dogs experienced cardiac dysrhythmias.

Our findings on improving hypercapnic depression of diaphragmatic contractility by administering dobutamine must be considered within the context of the study limitations. First, diaphragmatic contractility was induced by electrical stimulation of the phrenic nerves in this experiment, which differs from the response of respiratory muscles under more physiological conditions. Second, severe hypercapnic acidosis is rarely observed in patients with respiratory failure because of metabolic compensation of respiratory acidosis. However, we have already measured Pdi (as assessed by diaphragmatic contractility) at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation in dogs during severe hypercapnia (5). Third, we did not study the effects of discontinuing dobutamine on diaphragmatic contractility in the presence of hypercapnia. Still, we believe that our findings have important therapeutic implications for hypercapnic depression of diaphragmatic contractility. Further studies should consider these limitations.

In conclusion, dobutamine effectively improves hypercapnic depression of diaphragmatic contractility in an infusion rate-dependent manner in pentobarbital-anesthetized dogs.


   Footnotes
 
Accepted for publication July 17, 2007.

No sources of funding were used to assist in the preparation of this manuscript.

The authors have no conflicts of interest that are relevant to the content of this manuscript.


   REFERENCES
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Matthews AW, Howell JBL. Assessment of responsiveness to carbon dioxide in patients with chronic airway obstruction by rate of isometric inspiratory pressure development. Clin Sci Mol Med 1976;50:199–205[Web of Science][Medline]
  2. Rochester DF, Braun NMT, Arota NS. Respiratory muscle strength in chronic obstructive pulmonary diseases. Am Rev Respir Dis 1982;126:46–50[Web of Science][Medline]
  3. Juan G, Calverley P, Talamo C, Schnader J, Roussos C. Effect of carbon dioxide on diaphragmatic function in human beings. N Engl J Med 1984;310:874–9[Abstract]
  4. Howell S, Fitzgerald RS, Roussos CH. Effects of aminophylline, isoprotetrenol, and neostigmine on hypercapnic depression of diaphragmatic contractility. Am Rev Respir Dis 1985;132:241–7[Web of Science][Medline]
  5. Fujii Y. Comparative effects of dopamine and dobutamine on hypercapnic depression of diaphragmatic contractility in dogs. Pulm Pharmacol Ther 2004;17:289–92[Web of Science][Medline]
  6. Ide T, Kochi T, Isono S, Mizugichi T. Effect of sevoflurane on diaphragmatic contractility in dogs. Anesth Analg 1992;74:739–46[Abstract/Free Full Text]
  7. Fujii Y, Uemura A, Toyooka H. The recovery profile of reduced diaphragmatic contractility induced by propofol in dogs. Anesth Analg 2004;99:113–6[Abstract/Free Full Text]
  8. Fujii Y, Uemura A, Toyooka H. Midazolam-induced muscle dysfuntion and its recovery in fatigued diaphragm in dogs. Anesth Analg 2003;97:755–8[Abstract/Free Full Text]
  9. Macklem PT, Roussos C. Respiratory muscle fatigue: a cause of respiratory failure. Clin Sci Mol Med 1977;53:419–22[Web of Science][Medline]
  10. Roussos C, Macklem PT. The respiratory muscles. N Engl J Med 1982;307:786–97[Web of Science][Medline]
  11. Grassino A, Goldman MD, Mead J, Sears TA. Mechanics of the human diaphragm during voluntary contractions: statics. J Appl Physiol 1978;44:829–39[Abstract/Free Full Text]
  12. Yanos J, Wood LDH, Davis K, Keamy M. The effect of respiratory and lactic acidosis on diaphragm function. Am J Respir Dis 1993;147:616–9
  13. Fitzgerald RS, Hauer MC, Bierkamper GG, Raff H. Response of the in vitro rat diaphragm to changes in acid-base environment. J Appl Physiol 1984;57:1202–10[Abstract/Free Full Text]
  14. Katz AM, Hecht HH. The early ‘pump’ failure of the ischemic heart. Am J Med 1969;47:497–502[Web of Science][Medline]
  15. Nakamaru Y, Schwartz A. The influence of hydrogen ion concentration on calcium binding and release by skeletal muscle sarcoplasmic reticulum. J Gen Physiol 1972;59:22–32[Abstract/Free Full Text]
  16. Hermansen L. Effect of metabolic changes on force generation in skeletal muscle during maximal exercise. In: Porter R, Whelan J, eds. Human muscle fatigue: physiological mechanisms. Ciba Foundation Symposium No. 82. London: Pitman Medical, 1981:75–88
  17. Moxham J, Wiles CM, Newham D, Edwards RHT. Contractile function and fatigue of the respiratory muscle in man. In: Porter R, Whelan J, eds. Human muscle fatigue: physiological mechanisms. Ciba Foundation Symposium No. 82. London: Pitman Medical, 1981:197–205
  18. Edwards RHT. Physiological analysis of skeletal muscle weakness and fatigue. Clin Sci Mol Med 1987;54:463–70
  19. Jones DA, Bigland-Ritchie B, Edwards RHT. Excitation frequency and muscle fatigue: mechanical responses during voluntary and stimulated contraction. Exp Neurol 1979;64:401–13[Web of Science][Medline]
  20. Ebata T, Fujii Y, Toyooka H. Dobutamine increases diaphragmatic contractility in dogs. Can J Anaesth 1992;39:375–80[Web of Science][Medline]
  21. Robertson CH, Foster GH, Johnson RL. The relationship of respiratory failure to the oxygen consumption of, lactate production by, and distribution of blood flow among respiratory muscles during increasing inspiratory resistance. J Clin Invest 1977;59:31–42[Web of Science][Medline]
  22. Mas A, Saura P, Joseph D, Blanch L, Baigorri F, Artigas A, Fernandez R. Effects of acute moderate changes in PaCO2 on global hemodynamics and gastric perfusion. Crit Care Med 2000;86:360–5
  23. Hoffman BB. Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, eds. Goodman and Gilmann's the pharmacological basis of therapeutics. 10th ed. New York: McGraw-Hill, 2001:215–68




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2007 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press