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Effects of bilateral transvenous diaphragm pacing on hemodynamic function in patients after cardiac operations
J
THORAC CARDIOVASC SURG
1990;100:108-14
Effects of bilateral transvenous diaphragm pacing on hemodynamic function in patients after cardiac operations Experimental and clinical study The effects of bilateral transvenous diaphragm pacing and intermittent positive-pressure ventilation on hemodynamic function were compared by animal experiment in 18 dogs and by clinical study in 14 patients during the postoperative period after cardiac operations. Aortic, pulmonary arterial, right atrial, and left atrial pressures (transmural) and aortic flow were increased by diaphragm pacing in the canine experiment. In dogs with induced tricuspid insufficiency, aortic pressure, right and left atrial pressures, and aortic blood flow increased, similar to the results obtained in the clinical study. Diaphragm pacing produced a sufficient tidal volume (7.2 to 12 ml/kg) for maintenance of normal blood gas levels in the patients, all of whom recovered spontaneous breathing without any weaning problems after 2 to 6 hours of diaphragm pacing. The catheter electrode used for stimulation was placed 30 mm away from the sinus node to avoid arrhythmias. Respiratory control by diaphragm pacing is hemodynamically superior to that by intermittent positive-pressure ventilation, and its efficacy is expected, especially in critical cases or in diseases or conditions in which the decrease in the load of the right heart affects the hemodynamic status of the patient.
Kiyoshi Ishii, MD,a Hiromi Kurosawa, MD, Hitoshi Koyanagi, MD, Kiyoharu Nakano, MD, Naohide Sakakibara, MD, lkuo Sato, MD,b Makoto Noshiro, PhD,c and Mikio Ohsawa, MD,d Saga, Yamaguchi, Tokyo, and Shizuoka, Japan
Athough electrical stimulation of the phrenic nerve was first proposed by Hufeland I in 1783, it was Sarnoff and co-workers.i' who introduced the phrase electrophrenic respiration and studied it extensively. Long-term stimulation of the phrenic nerve became a clinical reality with the introduction of the radio-frequency transmission From the Department of Cardiovascular Surgery, Heart Institute of Japan, Tokyo Women's Medical College, Tokyo, Japan; the Department of Thoracic Surgery, Saga Medical School. Saga, Japarr': Sa to Clinic. Yamaguchi, Japan"; the Division of Electronic Engineering, Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Tokyo, Japan"; and the Department of Cardiovascular Surgery, Seirei Hamamatsu Hospital, Shizuoka, Japan," Received for publication March 29, 1989. Accepted for publication Aug. 21, 1989. Address for reprints: Kiyoshi Ishii, MD, Department of Thoracic Surgery, Saga Medical School, Nabeshima Sanbonsugi, Nabeshimacho, Saga. Saga Prefecture, Japan.
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system developed by Glenn and co-workers.s? who called the method diaphragm pacing. Diaphragm pacing has two major advantages over positive-pressure respiration: the pacer is implantable into the body and has favorable effects on the circulatory system. Although many investigations of diaphragm pacing have been done to provide implantable ventilatory support, only a few studies- 10, 11 have dealt with the temporary use of diaphragm pacing to avoid adverse effects of positive-pressure ventilation on the circulatory system. The purpose of this study was to examine experimentally and clinically whether diaphragm pacing or intermittent positive-pressure ventilation has more favorable effects on hemodynamic function. By means of animal experiment, we first examined the safety of bilateral transvenous electrical stimulation of the phrenic nerve and the effect of diaphragm pacing on the circulation. On the basis of the safety precautions established by our experience in this experiment, a clinical
Volume 100 Number 1
Diaphragm pacing
July 1990
10 9
Table I. Summary of clinical cases Diagnosis Pulmonic stenosis Tetralogy of Fallat Atrial septal defect Ventricular septal defect Ventricular septal defect with pulmonic stenosis Rupture of the sinus of Valsalva Aortic regurgitation Mitral stenosis Ischemic heart disease (aorta-coronary bypass) Ventricular aneurysm Total
No. of cases' I I 2 I I I I 4 I
.I
14
"Patient age: 16 to 56 years (average. 37.1 years). Patient weight: 35 to 63 kg (average. 52.7 kg).
study was then performed to confirm the effect of
diaphragm pacing. Materials and methods Experimental study. Eighteen adult mongrel dogs weighing 12 to IS kg were intravenously anesthetized with sodium pentobarbital (30 mg/kg). The battery-operated stimulator used in the experiments was designed and assembled in our laboratory. It delivered I msec capacitor-discharged biphasic pulses at a rate of 25 pulses per second. The amplitude of the pulses was modulated by a trapezoidal wave so that it produced a smooth diaphragm contraction similar to that in spontaneous respiration (Fig. I). The respiratory rate was 20 breaths/min, and the duration of inspiration was I second. Both the right and left phrenic nerves were simultaneously stimulated by insertion of a transvenous pacing catheter (cardiac-pacing Berkovit-Castillanos electrode, Hexa pola, USCI Div. of C.R. Bard, Billerica, Mass.) from the left external jugular vein. One pair of electrodes was positioned in the superior vena cava and the other pair in the left innominate vein. The output stage of the stimulator was divided into two parts, each of which was connected to each pair of electrodes, and electrically isolated from the other. Therefore the stimulating current flowed between the paired electrodes only, thus minimizing any dispersion of the current. Arrhythmia. Because a catheter electrode was placed near the sinus node in the superior vena cava, transvenous stimulation could possiblyelicit arrhythmias. In six dogs with the chest open, the minimum voltage that caused arrhythmias and the threshold voltage of diaphragm contraction were obtained for various distances (10 to 50 mm) between the catheter tip electrode and the sinus node (Fig. 2). This experiment was done with two different intervals between the electrodes. The position of the catheter tip was visually determined through the vesselwall, and the sinus node was assumed to be located at the junction of the superior vena cava and right atrium. Arrhythmia was detected as an irregular RR interval in the electrocardiogram, or a random change in arterial pressure, or both. Diaphragm contraction was confirmed by pneumotachography. Hemodynamic values. In 18 dogs the following variables were measured twice-while the animals were given intermittent positive-pressure ventilation with a Bird Mark ~ ventilator (Bird Products Corp., Palm Springs, Calif.) and while they were
OUTPUT
JlllllllL OUTPUT
Fig. 1. Block diagram of the stimulator. Waveforms in the blocks are schematically presented. The output voltage, inspiratory duration, and respiratory rate can be varied.
ventilated by diaphragm pacing: aortic pressure, pulmonary arterial pressure, left atrial pressure, right atrial pressure, intrathoracic pressure, aortic blood flow,and total pulmonary vascular resistance. These pressures and flow are represented herein by mean values. The aortic pressure reading was obtained with a catheter inserted from the femoral artery; other blood pressures.were recorded with three catheters inserted directly. Intrathoracic pressure was measured with a plastic tube inserted into the intrapleural space, and aortic blood flow was measured with an electromagnetic flowmeter, the probe of which was placed on the ascending aorta. Total pulmonary vascular resistance was obtained by dividing pulmonary arterial pressure by aortic blood flow. The first measurement was made approximately 30 minutes after the start of intermittent positive-pressure ventilation, and the second measurement was made about 30 minutes after the start of diaphragm pacing. Throughout the experiment, a hot-wire flowmeter monitored respiratory flow, and the tidal volume was obtairied from the flow by integration. Tricuspid insufficiency was created in six dogs to impose a load on the right atrium. Tricuspid insufficiency was created by cutting the chordae of the anterior papillary muscle with a hook that was inserted from the free wall of the right ventricle. Although the creation of tricuspid insufficiency rapidly worsened hemodynamic function, function reached a stable condition several minutes later. All measurements were performed after stabilization. Statistical analysis. The paired t test was used to examine the statistical significance of differences in hemodynamic function before and after diaphragm pacing in the same individual. Student's t test was used for comparisons between groups. The approximated values of the probability coefficient are given in the tables or figures or are mentioned in the text. Differences were considered to be significant at a p value of less than 0.05. Clinical study. Fourteen patients who had a cardiac operation (Table I) were studied. The same pacing catheter as that used in the canine experiment was introduced from the left basilic vein immediately after the operation. The position of the pacing catheter tip was confirmed by chest roentgenography after the patient had been moved to the intensive care unit. Two of the six pairs of electrodes were selected; one pair was positioned in the superior vena cava and the other in the left innominate vein. We withdrew the catheter slightly and sometimes had to select another pair to obtain the maximum
The Journal of
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Ishii et al.
vAL ® S-A node
Thoracic and Cardiovascular Surgery
QD Stimulation-current flows between the distal-tip and 6th electrode
Distance from Threshold Minimum Voltage Arrhythmia S-A node (rnm) Voltage (V) ~or arrhythmia(V) 10 20 30 35 40 50
0.46 0.73 0.73 0.65 0.72 0".58
± 0.06-* 1.1 ± 0.14 ± 0.32 1. 2 ± 0.22 ± 0,25 1.67± 0.25 ± 0.30 >3,1 (Max.) ± 0.23 >3,1 (Max,) ± 0.11 >3.1 (Max.)
*
aD S-A node
Mean
± SEM
+ + + (n=6)
Stimulation-current flows between the distal-tip and 2nd electrode
Distance from Threshold Minimum Voltage S-A node (mm) Vol rose (V) for arrhythmia(V) Arrhythmia 10 20 30 35 40 50
0.45 0,52 0.56 0.52 0.48 0,56
±0.04* ± 0.10 ± 0.12 ± 0.16 ± 0.09 ± 0.06
1. 2 ± 0.10 1.36 ± 0,38 ~ 3.1 (Max,) > 3.1 (Max.) > 3.1 (Max.) > 3.1 (Max,) *
Mean
± SEM
+ +
± (n=6)
Fig. 2. Effects of the position of the distal-tip electrode on the minimum voltage necessary for arrhythmias and the threshold voltage required for diaphragm contraction. A, Long distance between the electrodes; B, short distance between the electrodes. S-A. Sinoatrial. diaphragm contraction, but never pused the catheter, so that intrusion of the tip into the right atrium was avoided. During electrode positioning the patients were given intermittent positive-pressure ventilation with a Bennett MA-I respirator (Puritan-Bennett Corp., Overland Park, Kan.). After electrode positioning, measurements of hemodynamic function during intermittent positive-pressure ventilation included cardiac output, aortic pressure, left atrial pressure, right artrial pressure, and pulmonary arterial pressure. Diaphragm pacing was then started and hemodynamic function was measured 30 minutes later. Cardiac output was determined by the thermodilution technique with a Swan-Ganz catheter (Baxter Edwards Divisions, Irvine, Calif.). Aortic pressure was obtained with a catheter inserted from the radial artery; pulmonary arterial pressure with a Swan-Ganz catheter, and right arterial pressure and left arterial pressure were measured with other catheters inserted directly. In addition, arterial blood was analyzed periodically for assessment of blood gases. The respiratory rate was approximately 15 breaths/min. The tidal volume in respiration by-diaphragm pacing was the same as the tidal volume when carbon dioxide pressure showed a proper value under intermit-
tent positive-pressure ventilation respiratory control. The methods used for statistical comparisons of the data were the same as those in the canine experimental study. .
Results Arrhythmia. No arrhythmia was observed when the catheter tip (distal) electrode was positioned more than 30 mm away from the sinus node and when the applied voltage was less than or equal to 3.I V (Fig. 2). Supraventricular extrasystole or temporary atrial fibrillation was observed if the distance between the catheter tip and the sinus node was less than 30 mm, and ventricular extrasystole sometimes appeared when the catheter tip electrode entered the atrium. The minimum voltage required to cause arrhythmias was slightly higher for the shorter electrode interval. No voltage above 3.1 V was applied because the output of the stimulator was limited for safety reasons.
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Diaphragm pacing
July 1990
Table II. Changes in hemodynamic function produced by diaphragm pacing in normal dogs Intermittent positive-pressure ventilation
TPR (dyne/sec/cm- 5/m2)
82.9 ± 16.3 19.5±2.7 6.6 ± 2.1 10.5 ± 2.2 767 ± 167 1123 ± 344
RAPTM (mm Hg) LAP TM (mm Hg) PAPTM (mm Hg)
4.7 ± 1.6 7.6 ± 1.9 16.6 ± 2.7
AOP (m) (mm Hg) PAP (m) (mm Hg) RAP (m) (mm Hg) LAP (m) (mm Hg) AO-FLOW (ml/rnin)
Table III. Changes in hemodynamic function produced by diaphragm pacing in dogs with induced tricuspid insufficiency
Diaphragm pacing
101.3 ± 16.6 ± 4.0 ± 8.0 ± 908 ± 950 ±
16.9* 2.2* 2.0* 2.2* 174* 330t
11.4 ± 2.8t 12.5 ± 2.5t 23.1 ± 3.0t
AOP. Aortic pressure; PAP. pulmonary arterial pressure; RAP. right atrial pressure; l.AP. left atrial pressure (rn denotes mean and TM denotes transmural); AO-FLOW. aortic blood flow; TPR. total pulmonary vascular resistance. *1'<0.001. tl'
Hemodynamic data. Hemodynamic data obtained fromnormaldogsare summarizedin Table II. When the ventilation methodwasalteredfromintermittentpositivepressure ventilation to diaphragm pacing, all hemodynamic valires showed significant changes. Aortic blood flow increased by 18.4% and total pulmonary vascular resistance decreased by 20.1 %. Although pulmonaryarterial pressure, right atrial pressure, and left atrial pressure measured in relation to atmospheric pressure decreased, thesepressures measuredin relation to intrathoracic pressure (transmural pressures) rose. In the animalswith inducedtricuspidinsufficiency, the hemodynamic values changedin the same manneras that in the normalanimals (Table III). Aortic bloodflow was markedly increased by 36.8%. The relativechange [(data duringdiaphragmpacingminusdata during intermittent positive-pressure ventilationj/data during intermittent positive-pressure ventilation] in aortic blood flow was largerin the animalswith inducedtricuspidinsufficiency than in the normal animals (p < 0.05). Clinicalstudy. Diaphragmpacingreducedpulmonary arterialpressure, right atrial pressure, left atrial pressure, and total pulmonary vascular resistance and augmented cardiacoutput from 5.6 ± 1.4 (mean ± standard deviation) to 6.5 ± 1.1 L/min (Fig. 3). These results showed a similartendency to those in the canine experiment. All patients ventilated by diaphragm pacing soon recovered spontaneous respiration. The time requiredfor recovery varied from 2 to 6 hours (an average of 3.17 hours),and the tidal volume varied from 7.2 to 12 ml/kg (9.4 nil/kg). Blood gas levels were maintained at or near the normal level in all patients.
111
Intermittent positive-pressure ventilation
Diaphragm pacing
TPR (dyne/sec/cm- 5/m2)
75.8 ± 20.6 22.7 ± 2.0 13.9±1.5 8.1 ± 0.7 563 ± 158 1597 ± 529
93.3 ± 17.8* 20.8 ± 1.8t 12.0 ± I.7t 6.6 ± 0.6t 770±227t 1275 ± 410t
RAPTM (mm Hg) LAPTM (mm Hg) PAPTM (mm Hg)
12.8 ± 1.5 5.0 ± 1.1 19.8±2.2
17.5 ± 2.2t 12.6 ± 0.9t 25.9 ± 1.9t
AOP (m) (mm Hg) PAP (m) (mm Hg) RAP (m) (mm Hg) LAP (m) (mm Hg) AO-FLOW (ml/rnin)
For abbreviations see Table 11. *1' < 0.01. tl' < 0.001.
Discussion Significant improvements in hemodynamic function were observed during diaphragm pacing in both the animal and clinical experiments. Although Daggett, Piccinini,and Austen12 reported no significant improvements, they measured hemodynamic values during unilateral stimulation, whereas we used bilateral stimulation. As Glenn and co-workers stated," unilateral stimulation causesan uneven distributionof air, whichimplies uneven distribution of intrathoracic pressure. It is possible that such uneven intrathoracic pressurewould have obscured any improvements in hemodynamic function in the experiment by Daggett, Piccinini, and Austen. Positive-pressure respiration (intermittent or continuous) is now commonly used for ventilation in patients during operationand in the intensive care unit. However, this exertsadverse effects on the circulatorysystem,such as a decreasein cardiac output and an increasein pulmonary arterial pressure in relation to atmospheric pressure.U'!" In 1948 Cournand and associates'> found that the increaseof airway pressureby intermittent positive-pressure ventilation resulted in decreased filling pressure in the right ventricle and impeded systemic venous return. As a consequence low cardiac output appeared in accordance with Starling's law. Morgan and co-workers'< 14 reported that increased airway pressure raised intrathoracic pressure and hence lowered the difference between the right atrial and peripheral venous pressures, thus reducing cardiac output. Jardin and associates'? showed by echocardiography that the ventricular septum wasshifted to the left by positive end-ex-
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The Journal of Thoracic and Cardiovascular Surgery
Ishii et al.
CHANGES IN AOP, PAP, RAP PRODUCED BY DP (CLINICAL CASES) control
AOP(crean)
control
D P
PAP (crean)
control
D P
D P
RAP
~
I~I
100
10
50
~
50
25
IIii I
~
5
<,
------.
0
• p< 0.02
CHANGES IN LAP, C.O" control LAP
0
0
(rrunHg)
(rrunHg)
(rrunHg)
D P
•• p< 0.01
TPR PRODUCED BY DP (CLINICAL CASES)
C.O
control
control
D P
D P
TPR
1000
•
10
500 5
0 ....
.....1
OL(L/min)
(rrunHg)
• p< 0.01
...
OL-
.....
(dynes/s/cm-5/m2)
•• p
Fig. 3. Changes in hemodynamic function produced by diaphragm pacing (DP) in the clinical study. CO. Cardiac output; control means intermittent positive-pressure ventilation. For other abbreviations see Table II.
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Diaphragm pacing
July 1990
piratory pressure and hence restricted filling of the left ventricle, therefore reducing cardiac output. Our results agreed with those obtained by other researchers. In our animal experiment, transmural right atrial pressure and transmural left atrial pressure increased during diaphragm pacing. The study by Cournand and co-workers 15 suggests that the intrathoracic pressure decrease caused by diaphragm pacing increased transmural right atrial pressure and transmural left atrial pressure and that the increase in transmural right atrial pressure, which is the filling pressure of the right ventricle, resulted in the increase in cardiac output. The same theory applies to the left side of the heart because transmural left atrial pressure was also increased. Furthermore, the left-sided shift in the ventricular septum showed by Jardin and associates 16 would not have been caused by diaphragm pacing. The increase in aortic blood flow during diaphragm pacing in the animals with tricuspid insufficiency was attributable to the rise in transmural right atrial pressure, which reduced the regurgitant flow from the right ventricle. This finding suggests that diaphragm pacing is effective for increasing cardiac output even when the afterload to the right atrium is raised, because regurgitation resulting from tricuspid insufficiency is a type of right atrial afterload. We can thus infer that diaphragm pacing would serve to prevent a decrease in cardiac output after the Fontan operation. The Fontan operation raises the afterload in the following manner. In the normal case, the afterload is the diastolic pressure of the right ventricle, which is almost zero. However, the Fontan operation changes the afterload from diastolic pressure to pulmonary arterial pressure by anastomosis of the pulmonary artery to the right atrium. Because pulmonary arterial pressure is higher than the diastolic pressure, the afterload becomes larger after Fontan operations. Successful bilateral phrenic stimulation was reported by Daggett and co-workers! 7 and Wanner and Sackner, 18 who used two electrodes: one in the superior vena cava and the other in the left innominate vein. In our study the two pairs of electrodes were placed at the same positions as those in the study by Wanner and Sacker. 18 Our electrode configuration reduced dispersion of the stimulation current, and hence the possibility of arrhythmia, in comparison with the configuration by Wanner and Sacker. To prevent arrhythmia in the clinical study, we applied a stimulation of less than 3.1 V and placed the catheter tip electrode more than 30 mm away from the sinus node, on the basis of the results obtained in the canine experiment. Because stimulation of 2 to 2.5 V was sufficient to produce
1 13
the necessary tidal volume, the patients had full ventilation without arrhythmia. Sato and associates 19 and Kaneyuki and co-workers-" have reported that fatigue induced by diaphragm pacing was minimized by use of an alternating biphasic directional current and administration ofoxygen. In this study, capacitor-discharged diphasic pulses were used for the sake of convenience. However, in our previous study with the same waveform, I 0 tidal volume fell to only 70% of the initial value after 16 to 32 hours ofcontinuous stimulation applied to the phrenic nerve both transvenously and bilaterally. In this clinical study, such fatigue, which causes a fall in tidal volume and abnormality in blood gas levels, was never observed because the duration of diaphragm pacing was 2 to 6 hours and oxygen was administered. Because Glenn and associates-' recommended pacing of both sides of the diaphragm for 8 hours daily to avoid fatigue, the tidal volume should always be examined when the stimulation is prolonged beyond 6 hours. No thrombosis was observed in our study. However, further investigation is required to confirm that no thrombosis will result from the catheter remaining in the superior vena cava for any extended period of time. If a patient has anatomic variation of the left superior vena cava, it is impossible to stimulate the phrenic never bilaterally with a single catheter because a catheter introduced from the left basilicvein cannot reach the superior vena cava. We concluded that the practical indications of diaphragm pacing are limited. It is considered effective in critical cases in which the decrease in the load will increase cardiac output. REFERENCES 1. Hufeland CWo De usu vis electricae in asphyxia experimentis illustrato, Inauguraldissert. Gottingen: 1783. 2. Sarnoff SJ, Hardenbergh E, Whittenberger JL. Electrophrenic respiration. Am J Physiol 1948;155:1-9. 3. Sarnoff SJ, Whittenberger JL, Hardenbergh E. Electrophrenic respiration III. Mechanism of the inhibition of spontaneous respiration. Am J Physiol 1948;155:203-14. 4. Sarnoff SJ, Maloney JV Jr, Whittenberger JL. Electrophrenic respiration V. Effect on the circulation of electrophrenic respiration and positive pressure breathing during the respiratory paralysis of high spinal anesthesia. Ann Surg 1950;132:921-9. 5. Sarnoff SJ, Maloney JV Jr. Sarnoff LC, et al. Electrophrenic respiration in acute bulbar poliomyelitis: its use in management of respiratory irregularities. JAMA 1950; 143:1383-90. 6. Glenn WWL, Hageman JH, Mauro A, et al. Electrical stimulation of excitable tissue by radio-frequency transmission. Ann Surg 1964;160:338-45.
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7. Glenn WWL, Holcomb WG, Gee JBL, et al. Central hypoventilation; long-term ventilatory assistance by radiofrequency electrophrenic respiration. Ann Surg 1970;172:75573. 8. Glenn WWL, Gee JBL, Schachter EN. Diaphragm pacing: application to a patient with chronic obstructive pulmonary disease. J THORAC CARDIOVASC SURG 1978; 75:273-8 I. 9. Sato I, Kaneyuki T, Fujii Y, et al. Totally implantable diaphragm pacemaker: experimental studies. Surg Forum 1976:27:290-3. 10. Noshiro M, Suzuki S, Ishii K, et al. Bilateral transvenous diaphragm pacing in the postoperative period of open heart surgery. Digest of the combined meeting of the Twelfth International Conference on Medical and Biological Engineering and the Fifth International Conference on Medical Physiology 80.2, 1979. 1I. Ishii K, Irisawa A, Yamamoto N, et al. Effects on hemodynamics and ventilation of transvenous electrophrenic respiration in postoperative cardiac patients: experimental and clinical studies [in Japanese]. J Jpn Assoc Thorac Surg 1986;34:948-57. 12. Daggett WM, Piccinini JC, Austen WG. Intracaval electrophrenic stimulation. I. Experimental application during barbiturate intoxication, hemorrhage and ganglionic blockade. J THORAC CARDIOVASC SURG 1966;51:676-83. 13. Morgan BC, Martin WE, Hornbein TF, et al. Hemodynamic effects of intermittent positive pressure respiration. Anesthesiology 1966;27:584-90.
Thoracic and Cardiovascular Surgery
14. Morgan BC, Crawford EW, Guntheroth WG. The hemodynamic effects of changes in blood volume during intermittent positive-pressure ventilation. Anesthesiology 1969;30:297-305. 15. Cournand A, Motley HL, Werko L, et al. Physiological studies of the effects of intermittent positive pressure breathing on cardiac output in man. Am J Physiol 1948;152:162-74. 16. Jardin F, Farcot JC, Boisante L, et al. Influence of positive end-expiratory pressure on left ventricular performance. N Engl J Med 1981;304:387-92. 17. Daggett WM, Shanahan EA, Kazemi H, et al. Intracaval electrophrenic stimulation. II. Studies on pulmonary mechanics, surface tension, urine flow, and bilateral phrenic respiration. J THORAC CARDIOVASC SURG 1970;60:98-107. 18. Wanner A, Sackner MA. Transvenous phrenic nerve stimulation in anesthetized dogs. J Appl Physiol 1973;34:48994. 19. Sato G, Glenn WWL, Holcomb WG, et al. Further experience with electrical stimulation of the phrenic nerve: electrically induced fatigue. Surgery 1970;68:817-26. 20. Kaneyuki T, Hogan JF, Glenn WWL, et al. Diphragm pacing: evaluation of current waveforms for effective ventilation. J THORAC CARDIOVASC SURG 1977;74:109-15. 21. Glenn WWL, Holcomb WG, Shaw RK, et al. Long-term ventilatory support by diaphragm pacing in quadriplegia. Ann Surg 1976;183:566-77.
THORAC CARDIOVASC SURG
1990;100:108-14
Effects of bilateral transvenous diaphragm pacing on hemodynamic function in patients after cardiac operations Experimental and clinical study The effects of bilateral transvenous diaphragm pacing and intermittent positive-pressure ventilation on hemodynamic function were compared by animal experiment in 18 dogs and by clinical study in 14 patients during the postoperative period after cardiac operations. Aortic, pulmonary arterial, right atrial, and left atrial pressures (transmural) and aortic flow were increased by diaphragm pacing in the canine experiment. In dogs with induced tricuspid insufficiency, aortic pressure, right and left atrial pressures, and aortic blood flow increased, similar to the results obtained in the clinical study. Diaphragm pacing produced a sufficient tidal volume (7.2 to 12 ml/kg) for maintenance of normal blood gas levels in the patients, all of whom recovered spontaneous breathing without any weaning problems after 2 to 6 hours of diaphragm pacing. The catheter electrode used for stimulation was placed 30 mm away from the sinus node to avoid arrhythmias. Respiratory control by diaphragm pacing is hemodynamically superior to that by intermittent positive-pressure ventilation, and its efficacy is expected, especially in critical cases or in diseases or conditions in which the decrease in the load of the right heart affects the hemodynamic status of the patient.
Kiyoshi Ishii, MD,a Hiromi Kurosawa, MD, Hitoshi Koyanagi, MD, Kiyoharu Nakano, MD, Naohide Sakakibara, MD, lkuo Sato, MD,b Makoto Noshiro, PhD,c and Mikio Ohsawa, MD,d Saga, Yamaguchi, Tokyo, and Shizuoka, Japan
Athough electrical stimulation of the phrenic nerve was first proposed by Hufeland I in 1783, it was Sarnoff and co-workers.i' who introduced the phrase electrophrenic respiration and studied it extensively. Long-term stimulation of the phrenic nerve became a clinical reality with the introduction of the radio-frequency transmission From the Department of Cardiovascular Surgery, Heart Institute of Japan, Tokyo Women's Medical College, Tokyo, Japan; the Department of Thoracic Surgery, Saga Medical School. Saga, Japarr': Sa to Clinic. Yamaguchi, Japan"; the Division of Electronic Engineering, Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Tokyo, Japan"; and the Department of Cardiovascular Surgery, Seirei Hamamatsu Hospital, Shizuoka, Japan," Received for publication March 29, 1989. Accepted for publication Aug. 21, 1989. Address for reprints: Kiyoshi Ishii, MD, Department of Thoracic Surgery, Saga Medical School, Nabeshima Sanbonsugi, Nabeshimacho, Saga. Saga Prefecture, Japan.
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system developed by Glenn and co-workers.s? who called the method diaphragm pacing. Diaphragm pacing has two major advantages over positive-pressure respiration: the pacer is implantable into the body and has favorable effects on the circulatory system. Although many investigations of diaphragm pacing have been done to provide implantable ventilatory support, only a few studies- 10, 11 have dealt with the temporary use of diaphragm pacing to avoid adverse effects of positive-pressure ventilation on the circulatory system. The purpose of this study was to examine experimentally and clinically whether diaphragm pacing or intermittent positive-pressure ventilation has more favorable effects on hemodynamic function. By means of animal experiment, we first examined the safety of bilateral transvenous electrical stimulation of the phrenic nerve and the effect of diaphragm pacing on the circulation. On the basis of the safety precautions established by our experience in this experiment, a clinical
Volume 100 Number 1
Diaphragm pacing
July 1990
10 9
Table I. Summary of clinical cases Diagnosis Pulmonic stenosis Tetralogy of Fallat Atrial septal defect Ventricular septal defect Ventricular septal defect with pulmonic stenosis Rupture of the sinus of Valsalva Aortic regurgitation Mitral stenosis Ischemic heart disease (aorta-coronary bypass) Ventricular aneurysm Total
No. of cases' I I 2 I I I I 4 I
.I
14
"Patient age: 16 to 56 years (average. 37.1 years). Patient weight: 35 to 63 kg (average. 52.7 kg).
study was then performed to confirm the effect of
diaphragm pacing. Materials and methods Experimental study. Eighteen adult mongrel dogs weighing 12 to IS kg were intravenously anesthetized with sodium pentobarbital (30 mg/kg). The battery-operated stimulator used in the experiments was designed and assembled in our laboratory. It delivered I msec capacitor-discharged biphasic pulses at a rate of 25 pulses per second. The amplitude of the pulses was modulated by a trapezoidal wave so that it produced a smooth diaphragm contraction similar to that in spontaneous respiration (Fig. I). The respiratory rate was 20 breaths/min, and the duration of inspiration was I second. Both the right and left phrenic nerves were simultaneously stimulated by insertion of a transvenous pacing catheter (cardiac-pacing Berkovit-Castillanos electrode, Hexa pola, USCI Div. of C.R. Bard, Billerica, Mass.) from the left external jugular vein. One pair of electrodes was positioned in the superior vena cava and the other pair in the left innominate vein. The output stage of the stimulator was divided into two parts, each of which was connected to each pair of electrodes, and electrically isolated from the other. Therefore the stimulating current flowed between the paired electrodes only, thus minimizing any dispersion of the current. Arrhythmia. Because a catheter electrode was placed near the sinus node in the superior vena cava, transvenous stimulation could possiblyelicit arrhythmias. In six dogs with the chest open, the minimum voltage that caused arrhythmias and the threshold voltage of diaphragm contraction were obtained for various distances (10 to 50 mm) between the catheter tip electrode and the sinus node (Fig. 2). This experiment was done with two different intervals between the electrodes. The position of the catheter tip was visually determined through the vesselwall, and the sinus node was assumed to be located at the junction of the superior vena cava and right atrium. Arrhythmia was detected as an irregular RR interval in the electrocardiogram, or a random change in arterial pressure, or both. Diaphragm contraction was confirmed by pneumotachography. Hemodynamic values. In 18 dogs the following variables were measured twice-while the animals were given intermittent positive-pressure ventilation with a Bird Mark ~ ventilator (Bird Products Corp., Palm Springs, Calif.) and while they were
OUTPUT
JlllllllL OUTPUT
Fig. 1. Block diagram of the stimulator. Waveforms in the blocks are schematically presented. The output voltage, inspiratory duration, and respiratory rate can be varied.
ventilated by diaphragm pacing: aortic pressure, pulmonary arterial pressure, left atrial pressure, right atrial pressure, intrathoracic pressure, aortic blood flow,and total pulmonary vascular resistance. These pressures and flow are represented herein by mean values. The aortic pressure reading was obtained with a catheter inserted from the femoral artery; other blood pressures.were recorded with three catheters inserted directly. Intrathoracic pressure was measured with a plastic tube inserted into the intrapleural space, and aortic blood flow was measured with an electromagnetic flowmeter, the probe of which was placed on the ascending aorta. Total pulmonary vascular resistance was obtained by dividing pulmonary arterial pressure by aortic blood flow. The first measurement was made approximately 30 minutes after the start of intermittent positive-pressure ventilation, and the second measurement was made about 30 minutes after the start of diaphragm pacing. Throughout the experiment, a hot-wire flowmeter monitored respiratory flow, and the tidal volume was obtairied from the flow by integration. Tricuspid insufficiency was created in six dogs to impose a load on the right atrium. Tricuspid insufficiency was created by cutting the chordae of the anterior papillary muscle with a hook that was inserted from the free wall of the right ventricle. Although the creation of tricuspid insufficiency rapidly worsened hemodynamic function, function reached a stable condition several minutes later. All measurements were performed after stabilization. Statistical analysis. The paired t test was used to examine the statistical significance of differences in hemodynamic function before and after diaphragm pacing in the same individual. Student's t test was used for comparisons between groups. The approximated values of the probability coefficient are given in the tables or figures or are mentioned in the text. Differences were considered to be significant at a p value of less than 0.05. Clinical study. Fourteen patients who had a cardiac operation (Table I) were studied. The same pacing catheter as that used in the canine experiment was introduced from the left basilic vein immediately after the operation. The position of the pacing catheter tip was confirmed by chest roentgenography after the patient had been moved to the intensive care unit. Two of the six pairs of electrodes were selected; one pair was positioned in the superior vena cava and the other in the left innominate vein. We withdrew the catheter slightly and sometimes had to select another pair to obtain the maximum
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vAL ® S-A node
Thoracic and Cardiovascular Surgery
QD Stimulation-current flows between the distal-tip and 6th electrode
Distance from Threshold Minimum Voltage Arrhythmia S-A node (rnm) Voltage (V) ~or arrhythmia(V) 10 20 30 35 40 50
0.46 0.73 0.73 0.65 0.72 0".58
± 0.06-* 1.1 ± 0.14 ± 0.32 1. 2 ± 0.22 ± 0,25 1.67± 0.25 ± 0.30 >3,1 (Max.) ± 0.23 >3,1 (Max,) ± 0.11 >3.1 (Max.)
*
aD S-A node
Mean
± SEM
+ + + (n=6)
Stimulation-current flows between the distal-tip and 2nd electrode
Distance from Threshold Minimum Voltage S-A node (mm) Vol rose (V) for arrhythmia(V) Arrhythmia 10 20 30 35 40 50
0.45 0,52 0.56 0.52 0.48 0,56
±0.04* ± 0.10 ± 0.12 ± 0.16 ± 0.09 ± 0.06
1. 2 ± 0.10 1.36 ± 0,38 ~ 3.1 (Max,) > 3.1 (Max.) > 3.1 (Max.) > 3.1 (Max,) *
Mean
± SEM
+ +
± (n=6)
Fig. 2. Effects of the position of the distal-tip electrode on the minimum voltage necessary for arrhythmias and the threshold voltage required for diaphragm contraction. A, Long distance between the electrodes; B, short distance between the electrodes. S-A. Sinoatrial. diaphragm contraction, but never pused the catheter, so that intrusion of the tip into the right atrium was avoided. During electrode positioning the patients were given intermittent positive-pressure ventilation with a Bennett MA-I respirator (Puritan-Bennett Corp., Overland Park, Kan.). After electrode positioning, measurements of hemodynamic function during intermittent positive-pressure ventilation included cardiac output, aortic pressure, left atrial pressure, right artrial pressure, and pulmonary arterial pressure. Diaphragm pacing was then started and hemodynamic function was measured 30 minutes later. Cardiac output was determined by the thermodilution technique with a Swan-Ganz catheter (Baxter Edwards Divisions, Irvine, Calif.). Aortic pressure was obtained with a catheter inserted from the radial artery; pulmonary arterial pressure with a Swan-Ganz catheter, and right arterial pressure and left arterial pressure were measured with other catheters inserted directly. In addition, arterial blood was analyzed periodically for assessment of blood gases. The respiratory rate was approximately 15 breaths/min. The tidal volume in respiration by-diaphragm pacing was the same as the tidal volume when carbon dioxide pressure showed a proper value under intermit-
tent positive-pressure ventilation respiratory control. The methods used for statistical comparisons of the data were the same as those in the canine experimental study. .
Results Arrhythmia. No arrhythmia was observed when the catheter tip (distal) electrode was positioned more than 30 mm away from the sinus node and when the applied voltage was less than or equal to 3.I V (Fig. 2). Supraventricular extrasystole or temporary atrial fibrillation was observed if the distance between the catheter tip and the sinus node was less than 30 mm, and ventricular extrasystole sometimes appeared when the catheter tip electrode entered the atrium. The minimum voltage required to cause arrhythmias was slightly higher for the shorter electrode interval. No voltage above 3.1 V was applied because the output of the stimulator was limited for safety reasons.
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July 1990
Table II. Changes in hemodynamic function produced by diaphragm pacing in normal dogs Intermittent positive-pressure ventilation
TPR (dyne/sec/cm- 5/m2)
82.9 ± 16.3 19.5±2.7 6.6 ± 2.1 10.5 ± 2.2 767 ± 167 1123 ± 344
RAPTM (mm Hg) LAP TM (mm Hg) PAPTM (mm Hg)
4.7 ± 1.6 7.6 ± 1.9 16.6 ± 2.7
AOP (m) (mm Hg) PAP (m) (mm Hg) RAP (m) (mm Hg) LAP (m) (mm Hg) AO-FLOW (ml/rnin)
Table III. Changes in hemodynamic function produced by diaphragm pacing in dogs with induced tricuspid insufficiency
Diaphragm pacing
101.3 ± 16.6 ± 4.0 ± 8.0 ± 908 ± 950 ±
16.9* 2.2* 2.0* 2.2* 174* 330t
11.4 ± 2.8t 12.5 ± 2.5t 23.1 ± 3.0t
AOP. Aortic pressure; PAP. pulmonary arterial pressure; RAP. right atrial pressure; l.AP. left atrial pressure (rn denotes mean and TM denotes transmural); AO-FLOW. aortic blood flow; TPR. total pulmonary vascular resistance. *1'<0.001. tl'
Hemodynamic data. Hemodynamic data obtained fromnormaldogsare summarizedin Table II. When the ventilation methodwasalteredfromintermittentpositivepressure ventilation to diaphragm pacing, all hemodynamic valires showed significant changes. Aortic blood flow increased by 18.4% and total pulmonary vascular resistance decreased by 20.1 %. Although pulmonaryarterial pressure, right atrial pressure, and left atrial pressure measured in relation to atmospheric pressure decreased, thesepressures measuredin relation to intrathoracic pressure (transmural pressures) rose. In the animalswith inducedtricuspidinsufficiency, the hemodynamic values changedin the same manneras that in the normalanimals (Table III). Aortic bloodflow was markedly increased by 36.8%. The relativechange [(data duringdiaphragmpacingminusdata during intermittent positive-pressure ventilationj/data during intermittent positive-pressure ventilation] in aortic blood flow was largerin the animalswith inducedtricuspidinsufficiency than in the normal animals (p < 0.05). Clinicalstudy. Diaphragmpacingreducedpulmonary arterialpressure, right atrial pressure, left atrial pressure, and total pulmonary vascular resistance and augmented cardiacoutput from 5.6 ± 1.4 (mean ± standard deviation) to 6.5 ± 1.1 L/min (Fig. 3). These results showed a similartendency to those in the canine experiment. All patients ventilated by diaphragm pacing soon recovered spontaneous respiration. The time requiredfor recovery varied from 2 to 6 hours (an average of 3.17 hours),and the tidal volume varied from 7.2 to 12 ml/kg (9.4 nil/kg). Blood gas levels were maintained at or near the normal level in all patients.
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Intermittent positive-pressure ventilation
Diaphragm pacing
TPR (dyne/sec/cm- 5/m2)
75.8 ± 20.6 22.7 ± 2.0 13.9±1.5 8.1 ± 0.7 563 ± 158 1597 ± 529
93.3 ± 17.8* 20.8 ± 1.8t 12.0 ± I.7t 6.6 ± 0.6t 770±227t 1275 ± 410t
RAPTM (mm Hg) LAPTM (mm Hg) PAPTM (mm Hg)
12.8 ± 1.5 5.0 ± 1.1 19.8±2.2
17.5 ± 2.2t 12.6 ± 0.9t 25.9 ± 1.9t
AOP (m) (mm Hg) PAP (m) (mm Hg) RAP (m) (mm Hg) LAP (m) (mm Hg) AO-FLOW (ml/rnin)
For abbreviations see Table 11. *1' < 0.01. tl' < 0.001.
Discussion Significant improvements in hemodynamic function were observed during diaphragm pacing in both the animal and clinical experiments. Although Daggett, Piccinini,and Austen12 reported no significant improvements, they measured hemodynamic values during unilateral stimulation, whereas we used bilateral stimulation. As Glenn and co-workers stated," unilateral stimulation causesan uneven distributionof air, whichimplies uneven distribution of intrathoracic pressure. It is possible that such uneven intrathoracic pressurewould have obscured any improvements in hemodynamic function in the experiment by Daggett, Piccinini, and Austen. Positive-pressure respiration (intermittent or continuous) is now commonly used for ventilation in patients during operationand in the intensive care unit. However, this exertsadverse effects on the circulatorysystem,such as a decreasein cardiac output and an increasein pulmonary arterial pressure in relation to atmospheric pressure.U'!" In 1948 Cournand and associates'> found that the increaseof airway pressureby intermittent positive-pressure ventilation resulted in decreased filling pressure in the right ventricle and impeded systemic venous return. As a consequence low cardiac output appeared in accordance with Starling's law. Morgan and co-workers'< 14 reported that increased airway pressure raised intrathoracic pressure and hence lowered the difference between the right atrial and peripheral venous pressures, thus reducing cardiac output. Jardin and associates'? showed by echocardiography that the ventricular septum wasshifted to the left by positive end-ex-
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CHANGES IN AOP, PAP, RAP PRODUCED BY DP (CLINICAL CASES) control
AOP(crean)
control
D P
PAP (crean)
control
D P
D P
RAP
~
I~I
100
10
50
~
50
25
IIii I
~
5
<,
------.
0
• p< 0.02
CHANGES IN LAP, C.O" control LAP
0
0
(rrunHg)
(rrunHg)
(rrunHg)
D P
•• p< 0.01
TPR PRODUCED BY DP (CLINICAL CASES)
C.O
control
control
D P
D P
TPR
1000
•
10
500 5
0 ....
.....1
OL(L/min)
(rrunHg)
• p< 0.01
...
OL-
.....
(dynes/s/cm-5/m2)
•• p
Fig. 3. Changes in hemodynamic function produced by diaphragm pacing (DP) in the clinical study. CO. Cardiac output; control means intermittent positive-pressure ventilation. For other abbreviations see Table II.
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Diaphragm pacing
July 1990
piratory pressure and hence restricted filling of the left ventricle, therefore reducing cardiac output. Our results agreed with those obtained by other researchers. In our animal experiment, transmural right atrial pressure and transmural left atrial pressure increased during diaphragm pacing. The study by Cournand and co-workers 15 suggests that the intrathoracic pressure decrease caused by diaphragm pacing increased transmural right atrial pressure and transmural left atrial pressure and that the increase in transmural right atrial pressure, which is the filling pressure of the right ventricle, resulted in the increase in cardiac output. The same theory applies to the left side of the heart because transmural left atrial pressure was also increased. Furthermore, the left-sided shift in the ventricular septum showed by Jardin and associates 16 would not have been caused by diaphragm pacing. The increase in aortic blood flow during diaphragm pacing in the animals with tricuspid insufficiency was attributable to the rise in transmural right atrial pressure, which reduced the regurgitant flow from the right ventricle. This finding suggests that diaphragm pacing is effective for increasing cardiac output even when the afterload to the right atrium is raised, because regurgitation resulting from tricuspid insufficiency is a type of right atrial afterload. We can thus infer that diaphragm pacing would serve to prevent a decrease in cardiac output after the Fontan operation. The Fontan operation raises the afterload in the following manner. In the normal case, the afterload is the diastolic pressure of the right ventricle, which is almost zero. However, the Fontan operation changes the afterload from diastolic pressure to pulmonary arterial pressure by anastomosis of the pulmonary artery to the right atrium. Because pulmonary arterial pressure is higher than the diastolic pressure, the afterload becomes larger after Fontan operations. Successful bilateral phrenic stimulation was reported by Daggett and co-workers! 7 and Wanner and Sackner, 18 who used two electrodes: one in the superior vena cava and the other in the left innominate vein. In our study the two pairs of electrodes were placed at the same positions as those in the study by Wanner and Sacker. 18 Our electrode configuration reduced dispersion of the stimulation current, and hence the possibility of arrhythmia, in comparison with the configuration by Wanner and Sacker. To prevent arrhythmia in the clinical study, we applied a stimulation of less than 3.1 V and placed the catheter tip electrode more than 30 mm away from the sinus node, on the basis of the results obtained in the canine experiment. Because stimulation of 2 to 2.5 V was sufficient to produce
1 13
the necessary tidal volume, the patients had full ventilation without arrhythmia. Sato and associates 19 and Kaneyuki and co-workers-" have reported that fatigue induced by diaphragm pacing was minimized by use of an alternating biphasic directional current and administration ofoxygen. In this study, capacitor-discharged diphasic pulses were used for the sake of convenience. However, in our previous study with the same waveform, I 0 tidal volume fell to only 70% of the initial value after 16 to 32 hours ofcontinuous stimulation applied to the phrenic nerve both transvenously and bilaterally. In this clinical study, such fatigue, which causes a fall in tidal volume and abnormality in blood gas levels, was never observed because the duration of diaphragm pacing was 2 to 6 hours and oxygen was administered. Because Glenn and associates-' recommended pacing of both sides of the diaphragm for 8 hours daily to avoid fatigue, the tidal volume should always be examined when the stimulation is prolonged beyond 6 hours. No thrombosis was observed in our study. However, further investigation is required to confirm that no thrombosis will result from the catheter remaining in the superior vena cava for any extended period of time. If a patient has anatomic variation of the left superior vena cava, it is impossible to stimulate the phrenic never bilaterally with a single catheter because a catheter introduced from the left basilicvein cannot reach the superior vena cava. We concluded that the practical indications of diaphragm pacing are limited. It is considered effective in critical cases in which the decrease in the load will increase cardiac output. REFERENCES 1. Hufeland CWo De usu vis electricae in asphyxia experimentis illustrato, Inauguraldissert. Gottingen: 1783. 2. Sarnoff SJ, Hardenbergh E, Whittenberger JL. Electrophrenic respiration. Am J Physiol 1948;155:1-9. 3. Sarnoff SJ, Whittenberger JL, Hardenbergh E. Electrophrenic respiration III. Mechanism of the inhibition of spontaneous respiration. Am J Physiol 1948;155:203-14. 4. Sarnoff SJ, Maloney JV Jr, Whittenberger JL. Electrophrenic respiration V. Effect on the circulation of electrophrenic respiration and positive pressure breathing during the respiratory paralysis of high spinal anesthesia. Ann Surg 1950;132:921-9. 5. Sarnoff SJ, Maloney JV Jr. Sarnoff LC, et al. Electrophrenic respiration in acute bulbar poliomyelitis: its use in management of respiratory irregularities. JAMA 1950; 143:1383-90. 6. Glenn WWL, Hageman JH, Mauro A, et al. Electrical stimulation of excitable tissue by radio-frequency transmission. Ann Surg 1964;160:338-45.
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7. Glenn WWL, Holcomb WG, Gee JBL, et al. Central hypoventilation; long-term ventilatory assistance by radiofrequency electrophrenic respiration. Ann Surg 1970;172:75573. 8. Glenn WWL, Gee JBL, Schachter EN. Diaphragm pacing: application to a patient with chronic obstructive pulmonary disease. J THORAC CARDIOVASC SURG 1978; 75:273-8 I. 9. Sato I, Kaneyuki T, Fujii Y, et al. Totally implantable diaphragm pacemaker: experimental studies. Surg Forum 1976:27:290-3. 10. Noshiro M, Suzuki S, Ishii K, et al. Bilateral transvenous diaphragm pacing in the postoperative period of open heart surgery. Digest of the combined meeting of the Twelfth International Conference on Medical and Biological Engineering and the Fifth International Conference on Medical Physiology 80.2, 1979. 1I. Ishii K, Irisawa A, Yamamoto N, et al. Effects on hemodynamics and ventilation of transvenous electrophrenic respiration in postoperative cardiac patients: experimental and clinical studies [in Japanese]. J Jpn Assoc Thorac Surg 1986;34:948-57. 12. Daggett WM, Piccinini JC, Austen WG. Intracaval electrophrenic stimulation. I. Experimental application during barbiturate intoxication, hemorrhage and ganglionic blockade. J THORAC CARDIOVASC SURG 1966;51:676-83. 13. Morgan BC, Martin WE, Hornbein TF, et al. Hemodynamic effects of intermittent positive pressure respiration. Anesthesiology 1966;27:584-90.
Thoracic and Cardiovascular Surgery
14. Morgan BC, Crawford EW, Guntheroth WG. The hemodynamic effects of changes in blood volume during intermittent positive-pressure ventilation. Anesthesiology 1969;30:297-305. 15. Cournand A, Motley HL, Werko L, et al. Physiological studies of the effects of intermittent positive pressure breathing on cardiac output in man. Am J Physiol 1948;152:162-74. 16. Jardin F, Farcot JC, Boisante L, et al. Influence of positive end-expiratory pressure on left ventricular performance. N Engl J Med 1981;304:387-92. 17. Daggett WM, Shanahan EA, Kazemi H, et al. Intracaval electrophrenic stimulation. II. Studies on pulmonary mechanics, surface tension, urine flow, and bilateral phrenic respiration. J THORAC CARDIOVASC SURG 1970;60:98-107. 18. Wanner A, Sackner MA. Transvenous phrenic nerve stimulation in anesthetized dogs. J Appl Physiol 1973;34:48994. 19. Sato G, Glenn WWL, Holcomb WG, et al. Further experience with electrical stimulation of the phrenic nerve: electrically induced fatigue. Surgery 1970;68:817-26. 20. Kaneyuki T, Hogan JF, Glenn WWL, et al. Diphragm pacing: evaluation of current waveforms for effective ventilation. J THORAC CARDIOVASC SURG 1977;74:109-15. 21. Glenn WWL, Holcomb WG, Shaw RK, et al. Long-term ventilatory support by diaphragm pacing in quadriplegia. Ann Surg 1976;183:566-77.