Increase of Alveolar Pressure Reduces Systemic-to-Pulmonary Bronchial Blood Flow in Humans

Increase of Alveolar Pressure Reduces Systemic-la-Pulmonary Bronchial Blood Flow in Humans· Piergiuseppe Agostoni, M.D., F.C.C.R; Vincenzo Arena, M.D.;t lbolo Biglioli, M.D.;t Elisabetta Doria, M.D.; Andrea Saw, M.D.;t and Giuseppe Susini, M.D.*

We studied the effects of positive alveolar pressure (PA) on systemic to pulmooary bronchial blood Bow, Q.,...), in humans. The Q.,...) was measured during total cardiopulmooary bypass as the volume of blood accumulating in the left heart. This blood was vt;Dted by gravity from the left heart via a cannula introduced in the right upper pulmonary vein and advanced to the lowest portion of the left heart. In group A (n = 10) the Q.,...) was measured for 25 to 95 min with constant PA (4.0±0.1 em !isO, mean±SE). In group B (n= 10) Q.,...)was measured for!O min with PA=

4.1±0.2 em !isO and for a further !O min with PA= 14.1±0.4 em !IsO. The Q.,...) ranged between 0.31 and 1.76 percent of cardiac output (pump Bow) and remained constant with time (group A). The increase of PA from 4.1±0.1 to 14.1±0.4 em !isO reduced Q.,...) by -40 percent (p<0.01, group B). We conclude that positive PA reduces Q.,...)during total cardiopulmooary bypass. Therefore, we advise using low PA during assisted ventilation to preserve bronchial blood Bow. (Chat 1989; 96:1081-85)

in dogs and sheep have shown that bronchial Studies to the lung is reduced by PEEEI-4 a blood

was achieved using a standard technique. Blood Bowed from a twostage venous cannula (William Harvey extracorporeal cannula. 34 to 46 F Bard) introduced into the inferior vena cava and advanced into the right atrium. to an Os-heat exchanger (Oxy 41, Sorin), to the cardiopulmonary bypass pump (HL10, Cambro) and then, through the aortic cannula (21 to 24 F), back into the aorta. Proximal to the aortic cannula the aorta was clamped as was the pulmonary artery Through the right superior pulmonary vein a cannula (18 F) was placed in the lowest portion of the left heart. This usually was the left atrium. since the surgeon habitually lifted the cardiac apex to reach the inferoposterior surface of the heart. A second small cannula (8 F), open to atmospheric pressure. was placed, again through the right superior pulmonary vein into the left atrium. so that left atrial pressure was atmospheric. The larger left atrial cannula was connected to a calibrated cylinder placed -50 em below the level of the left atrium. The cylinder was connected through a stopcock to a roller pump by which the blood was propelled into the cardiotomy reservoir (Fig 1). The patients were cooled systemically and the heart was arrested with cardioplegic solution (-700 ml). During total cardiopulmonary bypass. the patients were not ventilated. The lungs were kept inJIated by a constant Row of air ranging between 4 and 8 Umin. The PA was set by adjusting an expiratory PEEP valve. Alveolar and systemic blood pressures. pump Bow (cardiac output). and esophageal and rectal temperatures were continuously monitored. Systemic to pulmonary bronchial blood Rovv, Qt.(s-p). was measured as the volume of blood returning to the left heart." This blood Rowed by gravity into the calibrated cylinder. where it was collected during the entire study for at least 3 min every 5 min. The mean Qt.(s-p) was calculated every 5 min. During the first 10 min of cardiopulmonary bypass. Qt.(s-p) was collected. but these measurements were always discarded because cardioplegic solution might be mixed with bronchial blood. Since during the surgical procedure the cardiac output (pump Row)was changed. depending on systemic blood pressure. Qt.(s-p) is reported both as absolute Rowand as a percentage of cardiac output. 11

How

technique frequently used during mechanical ventilation in patients with respiratory failure. A reduction of bronchial blood How may be deleterious for the survival of the lung parenchyma, particularly in some circumstances; eg, in the presence of lung injury, when pulmonary circulation may be compromised and bronchial blood How Increases.P" or in the presence of pulmonary embolism, when bronchial blood How is the major source of blood to the lung parenchyma. 8-10 However, it is not known whether a relationship between alveolar pressure and bronchial blood Ho~ similar to that observed in dogs and sheep, exists in humans. The present study was undertaken to investigate the effects of positive alveolar pressure (PA) on bronchial blood How in humans. MATERIAL AND METHODS

Twenty patients (17 men and three women) were studied while undergoing coronary artery bypass surgery for coronary artery disease. None had lung disease. heart failure. pulmonary hypertension (mean pulmonary artery pressure <20 mm Hg at preoperative cardiac catheterization). or congenital cardiac malformations. All provided written informed consent to both the surgical and experimental procedures. The study had been approved by the local ethics committee. The patients' ages were 60.6 ± 5.4 years (mean ± SD; range. 49 to 68 years). Total cardiopulmonary bypass *From the Istituto di Cardiologia. Istituto di Ricerche Cardiovascolari G. Sistni, CNR. UniversitA di Milano. Milan. Italy. tCattedra di Cardtochirurgia, UniversitA di Milano. *Uniti di Anestesia e Rianimazione. Fondazione I. Monzino, Milan. Ital~

Manuscript received February 6; revision accepted May 18. Reprint requuts: Dr. Guazzi, Centro de StUdio per le Ricerche CardiovascOlari del CNR, Via Bonfadini 214, 20138 Milan" Italy

Study Protocol In group A (n=10; mean age. 61.8±5.0 [SD] years) the ~.-p) CHEST I 98 I 5 I NOVEMBER, 1989

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FIGURE 1. Schematic diagram of circuit used to measure Qbr(I.P) during cardiopulmonary bypass. BA= bronchial artery, RA= right atrium, RV=right ventricle, LA=left atrium, LV=left ventricle, CC = calibrated cylinder, CR = circuit reservoir, O 2 - H EXC = Ol-heat exchanger, I = pulmonary and aortic clamps. See text for details.

was measured as described. Measurements were discontinued during rewarming of the patients, when esophageal temperature increased by more than ~c from the lowest esophageal temperature recorded during cardiopulmonary bypass. In group A, the PA was kept constant at 4.0±0.2 cm HID throughout the study.. In group B (n = 10, mean age 59.4 ± 6.0 (SD) years) the Qbr(I-P) was measured for 20 min with PA=4.1±0.2 em HID. Then PA was increased in a step-by-step fashion during 2 min to 14.1 ±O.~ em HID. While PA was constant (range 13 to 16 em H 20 ), the Qbr(I-P) was measured for a further 20 min. In three patients the duration of the cardiopulmonary bypass allowed us to reduce PAto 4.0±0.3 cm HID and to measure the Qbr(I-P) for an additional 10 min. Statistical Analysis

Data are reported as mean ± SE except as noted. In group B we tested the difference between the Qbr(S-P) measurements made during the last 5 min of collection with PA= 4.1 ± 0.2 cm HID and the four Qbr(I-P) measurements obtained with PA=14.1±0.4 cm H 20 . To do so we used the paired t test with the Bonferroni correction because multiple comparisons were made." Therefore, we accepted as significant p
FIGURE 2. Qbr(S-P) expressed as percentage of cardiac output for each patient in group A (n = 10). The Qbr(t-p)was measured for at least 3 min every 5-min period for the entire study. Qbr(t-p) at 5, 10, and 15 min are the mean ~S-p) measured between minutes 0 and 5, 5 and 10, and 10 and 15, respectively Dotted line=lack of data; PA= 4.0±0.2 cm H 20 , unchanged during the study.

RESULTS

Group A Qbr(s-p) was measured for an average period of 53.5 ± 6.2 min (range, 25 to 95 min). The Qbr(l-p) remained constant with time (Table I, Fig 2) and ranged between 0.32 and 2.76 percent of cardiac output (Fig 2). Mean systemic blood pressure, cardiac output (pump How), and esophageal and rectal temperatures were constant (Table I).

GroupB

During the first 20 min of the study, PAwas 4.1 ±0.2 em H 20 . Mean Qbr(s-p) ranged as absolute How between 44 ± 6 and 42 ± 4 mVmin (Table 2) and as percent of cardiac output between 1.54±0.22 and 1.69±0.22 (Fig 3 and 4). When PAwas elevated to 14.1 ±0.4 cm H 20 , the Qbr(l-p) fell in every patient but one (Fig 3). The mean Qbr(s-p) was 31±4 (1.13±0.16) and 27±5 (0.96±0.19) mVmin (percentage of cardiac output) in the first 5 min and between the 15th and 20th minute of PA elevation, respectively (p<0.01 compared with PA=4.1 cm H20 ; Table 2, Fig 4). Hemodynamic measurements and esophageal and rectal tempera-

Table 1-Group A: Hemodynamic MeaauremeRt8 and Temperatures, Mean (± SE)* TIme, min

5 No. Qbr(I-P)' mVmin Psa, mm Hg CO,Umin Tes,oC T rectum, °C

10

15

20

25

30

35

7 10 10 10 8 10 10 40 (4) 39 (5) 42 (5) 41 (5) 38 (5) 35 (5) 38 (4) 64.1 (3.9) 59.1 (3.6) 60.4 (3.8) 69.6 (3.5) 73.8 (3.6) 71.9 (5.1) 75.3 (4.1) 2.7 (0.2) 2.7 (0.2) 2.8 (0.2) 2.8 (0.2) 2.7 (0.2) 2.6 (0.2) 2.3 (0.2) 26.7 (0.5) 26.7 (0.4) 26.8 (0.7) 26.8 (0.3) 27.0 (0.4) 26.8 (0.2) 26.7 (0.3) 29.9 (0.6) 29.8 (0.6) 29.3 (0.5) 29.3 (0.4) 28.8 (0.4) 28.9 (0.5) 28.6 (0.5)

40 34 72.0 2.3 26.6 28.3

6 (5) (6.1) (0.2) (0.4) (0.5)

45

37 77.8 2.3 26.9 28.2

6 (5) (8.5) (0.2) (0.5) (0.5)

50

36 64.8 2.3 27.8 28.8

5 (6) (2.8) (0.3) (0.6) (0.4)

*Qbr(,.P) = mean systemic to pulmonary bronchial blood flow; Psa = mean systemic blood pressure; CO = cardiac output (pump flow); Tes, T rectum = esophageal and rectal temperatures.

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Systemic-to-Pulmonary Bronchial BloodFlow (Agostoni at 81)

Table 2-Group B: Hemodynamic Measurements and Temperatures, Mean (± SE)* PA 4.1 ±0.2 cm H 2O

Time, min No. Qbr(I"P)t mllmin Psa, mm Hg COtUmin Tes, °C T'rectum, °C

5 10 44 (6) 62 (3.3) 2.9 (0.1) 27.0 (0.1) 29.1 (0.3)

10 10 43 (5) 62 (4.5) 2.7 (0.1) 26.9 (0.2) 28.8 (0.3)

14.1 ± 0.4 cm H 2O

15 10 44 (4) 63 (4.1) 2.7 (0.1) 26.9 (0.2) 28.7 (0.3)

20 10 42 (4) 65 (3.8) 2.6 (0.1) 27.0 (0.3) 28.7 (0.3)

5 10 31*(4) 66 (3.2) 2.7 (0.1) 27.1 (0.3) 28.7 (0.3)

10 10 28*(4) 62 (2.9) 2.7 (0.1) 27.3 (0.3) 28.7 (0.3)

15 10 27*(4) 66 (3.3) 2.7 (0.2) 27.6 (0.4) 28.8 (0.3)

20 10 27*(5) 67 (3.3) 2.8 (0.2) 28.2 (0.4) 29.1 (0.3)

*Qbr(I"P) = mean systemic to pulmonary bronchial blood flow; Psa = mean systemic blood pressure; CO = cardiac output (pump flow); Tes, T rectum = esophageal and rectal temperatures. tp
tures were constant (Table 2). In the three (patients 12, 13, and 15, Fig 3) in whom it was possible to reduce PA to -4 cm H 20, the mean ~r(s-p) was 1.28±0.12 (PA=4.1±0.0 cm H 20), 0.74±0.09 (PA= 14.2±0.1 cm H 20), and 1.22±0.09 (PA=4.0± 0.1 cm H 20) percent of cardiac output. DISCUSSION

In this study systemic-to-pulmonary bronchial blood flow; Qbr(s-p), was measured in humans during total cardiopulmonary bypass. The ~r(s-p), both as absolute flow and as a percentage of cardiac output, remained constant as long as alveolar pressure (PA) was constant; the increase in PA reduced Qbr(s-p) in a significant manner. To measure ~s-p), we used a technique similar to that previously described by Baile et ale 11 Unlike those

2.5

authors, we clamped the pulmonary artery to prevent blood leakage through the pulmonary valve and blood flowfrom the right heart to the pulmonary circulation. Theoretically this could happen secondary to increased alveolar and right heart pressures, the latter due to incomplete blood drainage from the right atrium. The ~r(s-p) measurements did not prolong the surgery or interfere with the surgical procedure. Q br(s-p) was stable over a wide range of time from 25 to 95 min (Fig 2) and was in the same range of that reported by Baile et al" on humans without lung diseases during total cardiopulmonary bypass and by other authors on different animal species. 1.8.13.14.15 Even though none of the patients who participated in our study had clinical lung disease, the relatively wide Q br(s-p) range reported (Fig 2 and 3) might be due to subclinical lung impairment." Indeed, only 4/20 patients were nonsmokers (patients 2, 3, 11, and 17; Fig 2 and 3), and nonsmokers tended to have lower flows. 11 The ~r(s-p) was not measured during the first 10 min 2.5

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FIGURE 3. QbI(l-P) expressed as percentage of cardiac output for each patient in group B (n = 10). The QbI(."P) was measured for 20 min with PA=4.1±0.2 em H,O (left) and for 20 more min with PA=14.1±0.4 em HID (right).. As in Figure 2 t QbI(l-p) at 5 t lOt 1St and 20 min are the mean QbI(l-p) measured between minutes oand 5 t 5 and lOt 10 and 15t and 15 and 20 t respectively.

5

10

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20

15 20 minutes

FIGURE 4. Mean ± SE of Qbr(I"P) expressed as percentage of cardiac output in group B. TIme intervals as in Figure 3. *p
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of cardiopulmonary bypass. This was necessary because some cardioplegic solution injected into the aortic root might drain into the left atrium via thebesian veins and therefore might be vented mixed with bronchial blood. Flow of cardioplegic solution through the coronary vessels is present for only a short time after the cardioplegic solution injection, when aortic root pressure (proximal to aortic clamp) is greater than left and right atrial pressures. We judged that after a few minutes, aortic root pressure should be returned to zero, as suggested by the visual regression of aortic root distention, and that consequently the flow of cardioplegic solution into the left atrium should be negligible. Different factors may influence the ~S-P) during total cardiopulmonary bypass including the surgical procedure," body temperature.v'" and the hemodynamic status. 16 The surgical procedure was similar in all of the patients and therefore should equally influence groups A and B. Body temperature was unphysiologically low It is known that a reduction of body temperature reduces Qbr(s_p).8 Therefore, to avoid the effects of body temperature changes on Qbr(I_p),8,13 we continuously monitored esophageal and rectal temperatures and report only those measurements obtained during stable thermal conditions (Tables 1 and 2). Systemic blood pressure and cardiac output influenced Qbr(l-p), as demonstrated by experimental studies.14,17,18 However, in our study changes in the hemodynamic status were negligible during total cardiopulmonary bypass (Tables 1 and 2). Nonetheless, we have taken into account the possible effects of cardiac output (pump flow) changes on ~s-p) by reporting ~s-p) both as absolute flow and as percentage of cardiac output (pump flow). Our method measures the portion of bronchial blood flow that drains into the pulmonary circulation and does not account for the portion that drains, via bronchial veins, into the azygos vein. It is widely accepted that bronchial blood flow to all the lung parenchyma (intrapulmonary bronchi and lung tissue) drains via the pulmonary circulation into the left atrium, that it is the sole bronchial blood flow significantly reduced by positive PA in animals,' and that it is 80 percent of total bronchial blood flo~ 1,8.13-15.19 This partitioning of left and right drainage of bronchial circulation is not affected by the presence or the absence (as in our study) of pulmonary blood flo~8 The PA was -4 cm H 20 during control conditions (group A and first 20 min in group B). This is the standard PA applied at our Institute during cardiopulmonary bypass to prevent pulmonary atelectasis. The value 14 em H 20 (group B second part of the study) was chosen because it is an end-expiratory pressure frequently reached in patients during mechanical ventilation and is also the mean end-expiratory pres1084

sure previously used in animal studies to evaluate the effects of elevated PA on ~s-p). 1-4 Particularly with elevated PA, some of the bronchial blood flow pooled in the lungs might cause pulmonary vasculature distention and edema. When a technique similar to ours is used on dogs, the possible accumulation or loss of fluids in the lung is measured as lung weight changes and considered in the calculation of bronchial blood flo~ 1,3.5,7,8.10.13,14 Although we were unable to measure lung weight changes, we believe it is unlikely that lung fluids changed during our measurements. In fact, this study was performed while the lungs were in zone 1 (PA>pulmonary vascular pressures), and it has been shown during in vioo experiments that in zone 1, lung weight was constant when PA changes similar to ours were used." Therefore, we think that our measurements of ~s-p) probably represent the entire Qbr(I-P). The effects of positive PA on bronchial blood flow to the lung in humans during assisted ventilation remain unknown. Our study shows that positive PA reduces bronchial blood How to the lung during total cardiopulmonary bypass. The study of the mechanisms responsible for the bronchial blood flow reduction due to increased alveolar pressure is beyond the purpose of the present work. However, a reduction of bronchial blood flow driving pressure as well as an active or passive increase ofbronchovascular resistance may be suggested. Our study strengthens previous observations obtained in experimental animals!" and allows us to suggest a reduction of bronchial blood flow to the lung during assisted ventilation with positive PA in humans. A bronchial blood How reduction may be clinically relevant in case of pulmonary embolism when bronchial blood How is the major source of blood to the lung parenchyma." It may also have some importance in ARDS, when pulmonary blood How to injured lung regions decreases and bronchial blood flowincreases.s" In both cases a reduction of bronchial blood How by positive PA may be deleterious for the healing of the lung parenchyma." Hence, we suggest that the lowest PA, and therefore PEE~ for adequate systemic blood oxygenation should be used during assisted ventilation to preserve bronchial blood How: ACKNOWLEDGMENTS: ~ thank Mrs Patrizia De Padova, Mrs Anna Ferrario, and Mrs Fabiana Rossi for their excellent technical assistance.

REFERENCES 1 Baile EM, Albert RIC, Kirk w Lakshminarayan S, Wiggs BJR, Pare PD. Positive end-expiratory pressure decreases bronchial blood 80w in the dog. J Appl Physioll984; 56:1289 2 Cassidy SS, Haynes MS. The effects of ventilation with positive end-expiratory pressure on the bronchial circulation. Bespir Physioll987; 66:269 3 Charan NB, Albert RIC, Lakshminarayan S, Kirk ~ Butler J. Factors affecting bronchial blood 80w through bronchopulmonary anastomoses in dogs. Am Rev Respir Dis 1986; 134:85 4 Wagner EM, Mitzner WA, Bleeker ER. Effects of airway Systemic-to-Pulmonary Bronchial Blood Flow (AQostonIet aI)

pressure on bronchial blood How J Appl Physioll987; 62:561 5 Deffebach ME, Lakshminarayan S, Kirk Butler J. The bronchial circuJation and cyclo-oxygenase products in acute lung inj~ J Appl Physioll987; 63:1083 6 Greene R, Zapol WM, Snider MT, Reid L, Snow R, O'Connel RS, et ale Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis 1981; 124:593 7 Lakshminarayan S, Jindal SIC, Kirk WIC,Butler J. Acute increase in anastomotic bronchial systemic to pulmonary blood How due to generalized lung injury. J Appl Physioll987; 62:2358 8 Agostoni PG, DefJebach ME, Kirk ~ Mendenhall JM, Albert RIC, Butler J. Temperatures alters bronchial blood Howresponse to pulmonary artery obstruction. J Appl Physioll987; 62:1907 9 Dalen J, Haffajee C, Alpert J, Howe J, Ockene I, Paraskos J. Pulmonary embolism, pulmonary hemorrhage and pulmonary infarction. N Engl J Med 1977; 296:1431 10 Jindal SIC, Lakshminarayan S, Kirk ~ Butler J. Acute increase in anastomotic bronchial blood How after pulmonary artery obstruction. J Appl Physioll984; 57:424 11 Baile EM, Ling H, Heyworth JR, Hogg JC, Pare PD. Bronchopulmonary anastomotic and non-coronary collateral blood How

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in humans during cardiopulmonary bypass. Chest 1985; 87:749 12 Wallenstein S, Zuclcer CL, Fleiss JL. Some statistical methods useful in circulation research. Cire Res 1980; 47:1 13 Agostoni PC, Deffebach ME, Kirk ~ Brengelmann GL. Temperature dependence of intraparenchymal bronchial blood How Respir Physioll987; 68:259 14 Agostoni PC, Deffebach ME, Kirk ~ Lakshminarayan S, Butler J. Upstream pressure for systemic to pulmonary How from bronchial circulation in dogs. J Appl Physioll987; 63:485 15 DefJebach ME, Charan NB, Lakshminarayan S, Butler J. The bronchial circuJation: small but a vital attribute to the lung. Am Rev Respir Dis 1987; 135:463 16 Bruner HD, Schmidt CF. Blood How in the bronchial artery of anesthetized dog. Am J Physioll947; 148:648 17 Auld PAM, Rudolph AM, Golinko RJ. Factors affecting bronchial collateral Howin dog. Am J Physioll960; 198:1166 18 Modell HI, Beck IC, Butler J. Functional aspects of canine bronchial-pulmonary vascular communications. J Appl Physiol 1981; 50:1045 19 Baile EM, Nelems JMB, Schulzer ~ Pare PD. Measurements of regional bronchial arterial blood How and bronchovascular resistance in dogs. J Appl Physioll982; 53:1044

Cardiology 'go-Pearls for the Clinician The Cardiovascular Institute of Scripps Memorial Hospitals will present this program at the La Jolla Marriott Hotel, La Jolla, California, January 25-27. For information, contact Nancy Donegan, Deverman and Associates, 7777 Alvarado Road, Suite 110, La Mesa, California 92041 (619:462-6800).

CHEST I 98 I 5 I NOVEMBER. 1989

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