Barcelos, C. S.

Messmer, Konrad

Schosser, Rudolf

Vidal-Melo, M. F.

Zwißler, Bernhard

English

Universität München: Elektronischen Publikationen

Brazilian J Med Biol Res (1993) 26:37-42 ISSN0100-879X 
Short Communication
Heterogeneity of left ventricular perfusion during 
pulmonary edema and microembolism treated 
with positive end-expiratory pressure and 
norepinephrine 
M.E Vidal~Melo\ R. Schosser2, 
CS. Barcelos1, B. Zwissler3 
and K. Messmer3 
1Programa de Engenharia Biomädica, COPPE, 
Universidade Federal do Rio de Janeiro, 21945-970 Rio de Janeiro, RJ, Brasil 
2Abteilung fuer Experimentelle Chirurgie, Universitaet Heidelberg, W-6900 Heidelberg, Germany 
3Institut fiier Chirurgische Forschung, Universitaet Muenchen, W-8000 Muenchen, Germany 
Regional left ventricular myocardial blood flow was studied in an experimental model of 
pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure 
(PEEP)* The analysis was based on a 3-dimensional extension of the autocorrelation function used to 
assess the spatial correlation ( r ^ ) of myocardial perfusion. Experiments were performed on 8 
premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 
mg/kg) and glass beads. Successive PEEP values of 10, IS and 20 cm H^O (P20) were applied and 
norepinephrine (NE, 0.2-1.0 pg min"1 kg"1) was administered after P20. Regional perfusion was 
measured with radioactive microspheres. The left ventricle (LV) was dissected into 2S6 samples, 
was computed as the correlation of regional perfusions of samples ρ units apart in the apex-to-base, 
endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation 
(control, C) , P20 and NE. Control values of r ^ were around 50% in the apex-to-base and angular 
directions and the sign was inverted in the endo-epicardial direction. A reduction of r ^ to values close 
to zero was observed in all directions for P20 and NE. This is the typical pattern of independent 
distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree 
of neighborhood dependence of regional L V myocardial blood flow. This dependence is not observed 
under PEM, mechanical ventilation with PEEP and NE. 
Key words: autocorrelation, perfusion, left ventricle, microspheres, myocardial perfusion, blood flow 
heterogeneity. 
Presented at the VII Annual Meeting of the Federaf äo de Sociedades de Biologia Experimental, Caxambu, MG, 
August 26-29,1992. 
Correspondence: M.F. Vidal-Melo, Programa de Engenharia Biomedica, COPPE, Universidade Federal do Rio de 
Janeiro, Caixa Postal 68510,21945-970 Rio de Janeiro, RJ, Brasil. 
38 Μ.F. Vtdal-Meloetal. 
The presence of myocardial blood flow heterogeneity (MBFH) under 
physiological and pathological conditions is an established concept. Several 
methods have been used to express this heterogeneity as statistical parameters 
(e.g., coefficient of variation (1)) or by graphic approaches (e.g., histograms 
(2,3) and density functions (4)). 
It has been shown that changes of MBFH occur under different 
pathophysiological conditions (1,2,5). It might be hypothesized that these 
changes are accompanied by changes of the 3-dimensional neighborhood 
dependences or spatial correlation of blood flow. However, none of the usual 
techniques for quantification of MBFH permits the study of this variable. 
In the present report we use an expanded concept of the autocorrelation 
function, a technique employed in signal processing, to analyze left ventricular 
myocardial blood flow in an experimental model of pulmonary edema and 
microembolization (PEM) ventilated with positive end-expiratory pressure 
(PEEP) and pharmacologically treated with norepinephrine (NE). 
Experiments were performed on 8 foxhounds (18 ± 2 kg) premedicated 
with 1.5-2.0 ml propiomazine, anesthetized with 20 mg/kg pentobarbital 
sodium, 0.75 mg/kg piritramid and 0.25 mg/kg alcuronium iv and maintained 
by continuous infusion of pentobarbital (5 mg kg"1 h*1). Ringer solution was 
administered at a rate of 5 ml kg"1 h"1 throughout the experiment. The dogs were 
intubated and mechanically ventilated (FI0 2 s 100%, 12 cpm). Tidal volumes 
were adjusted to keep P e tC0 2 between 35 and 45 mmHg. 
After surgical preparation, the animals were isovolemically hemodiluted 
with 6% dextran 60 to a hematocrit of 28% and allowed to stabilize for 30 min, 
after which control measurements (C) were performed. Experimental PEM was 
produced with oleic acid (0.01 ml/kg) and glass beads (100 μιη diameter) as 
previously described (6). After at least 70 min of stabilization, PEEP was 
increased progressively to 10,15 and 20 cm H 2 0 (P20). Finally, norepinephrine 
(NE) was administered (0.2-1.0 pg kg"1 min"1) while PEEP was maintained at 
20 cm I^O. 
Organ blood flow was measured with NEN-TRAC microspheres 
(diameter 16.5 ± 0.1 μπι) labeled with 141Ce, 5 1Cr, 1 0 3Ru, 1 1 4 In , 46Sc or 9 5Nb, 
injected into the left atrium (average of 40,000 particles/kg) within a period of 
30 s. The arterial reference blood sample was drawn from the right femoral 
artery over 3 min at a rate of 3.24 ml/min. The regional myocardial blood flow 
was analyzed after C, P20 and NE. 
The dissection scheme for the left ventricle (LV) is shown in Figure 
1. After fixing the heart in 6% formaldehyde for 1 week, the atria were removed 
and the heart was dissected into 10 slices perpendicular to its axis, beginning 
Brazilian J Med Biol Res 26(1) 1993 
Regional ventricular myocardial bloodflow 39 
Figure 1 - Dissection scheme of left ventricular myocardium. 
at the base. Slices 1-8 were subdivided into LV, right ventricle and septum. LV 
free wall and septum were considered to constitute the LV. Each LV slice was 
cut into 8 segments and further subdivided into 4 layers, resulting in 256 
samples. 
Spatial correlation (r t) was determined on the basis of an extension 
of the digital autocorrelation function estimate (7) to the 3-dimensional case. 
As used in this study, it provides the correlation of the relative perfusion (RP) 
of samples ρ units apart. Thus, when ρ s 0, r t s 1. Correlations were computed 
with ρ varying in the endo-epicardial (r = 1,4, layers), angular (a = 1,8, sectors) 
and apex-to-base (h s 1,8, slices) directions. 
Brazilian J Med Biol Res 26(1) 1993 
40 Μ. F. Vtdal-MeloetaL 
The r s p a t estimate for each displacement ρ in a given direction was 
computed as: 
•y direction 
r
S p a t (p) = - 7 ; CD 
Vglobal 
where: 
rah w (2) R R . . -
^rah 
j N f N , N h 
R P ' N ^ I l R P r a h (3) 
x ^ r=l a=l h=l 
Ν, N 8 N h 
V g i o b a ^ I I I ^ r a h - R P V 
r^l a5*! h«l 
(4) 
Ν , - ρ N , N h 
Vi = ^ 7 ± : Σ I I C R P r a h - R P K R P i r ^ a h - R P ) (5) 
L y t Ρ r-l a-lh-1 
N , N , N h 
* Σ IXCRPrah " RPXRPra p h " (6) 
r-l a-1 h-1 
N r N a N h - p 
V P H
 =ΤΤΤΣΣ Σ ^ - ^ Χ ^ ί Κ . ρ ) - ^ ) (7) 
i N h Ρ r-l a-1 h-1 
Ν = total number of samples; N r = number of layers; N a = number of sectors; N h = 
number of slices; = blood flow measured in sample with coordinates rah; 
= weight of sample with coordinates rah; ap = a + ρ for (a + p)<Na; ap = a + ρ - N a for (a 
+ p)>Na; V g l o b a l ä global variance of relative perfusion; V ,̂ V* and ν£ β covariance 
of relative perfusions of samples ρ units apart in the directions r (layers), a (sectors) 
and h (slices), respectively. 
Brazilian J Med Biol Res 26(1) 1993 
Regional ventricular myocardial bloodflow 41 
The coefficients of variation of RP for the C, P20 and NE experimental 
points were 25.2 ± 5.2%, 20.5 ± 3.3% and 18.4 ± 3.8% (P<0.05 for pairwise 
comparisons). Plots of spatial correlation (r t) against ρ in angular direction are 
shown in Figure 2A for C, P20 and NE. Curves are symmetrical in relation to 
ρ = 4. Note that the NE curves fall to values closer to 0 than C curves as ρ 
increases. P20 assumes intermediate values. This reduction to 0 of P20 and mainly 
NE can also be observed in Figure 2B for the apex-to-base direction. 
Figure 2C shows plots of r ^ for radial direction. For ρ • 1 no 
distinction between C, P20 and NE is observed. At ρ - 2 and more clearly for 
ρ = 3 there is a separation between C values, which become negative, and P20 
and NE values, which remain close to 0. 
-0.5 I ι ι , ι ι » • 
0 1 2 3 4 5 6 7 
P-Sector 
P-Laycr 
-0.5 I " « « " ·——' 
0 1 2 3 4 5 6 7 
P-Slice 
Figure 2 - Plots of the spatial autocorrelation 
function for control (circles), PEEP of 20 cm 
HjO (triangles) and norepinephrine (squares). 
Data are reported as means ± SD. A: Angular 
direction. Note the reduction to zero for NE; 
Β: apex-to-base direction. Note the faster re­
duction to zero for NE followed by P20; C: 
endo-epicardial direction. Note that control 
values change sign and assume negative val­
ues. This is related to the presence of a depen­
dent endo-epicardial perfusion gradient. 
Curves for P20 and N E drop to values near 
zero. *P<0.05 for the test of equality of all 
three points at a given p; *P<0.05 for compari­
son between C and NE (Friedman's test). 
Brazilian J Med Biol Res 26(1) 1993 
42 M.F. Vidal-MeloetaL 
Recently, van Beek et al. (8) proposed a method for estimating spatial 
correlation using fractal dimension. Austin Jr. et al. (5) used auto-correlation in 
a 2-dimensional approach, without considering direction, to assess local conti­
nuity. In the present study we present a method based on autocorrelation which 
considers direction and permits direct computation of the degree of 3-dimensional 
neighborhood dependence of LV myocardial perfusion. 
In the apex-to-base and angular directions, the results show higher 
correlations of relative perfusion among regions for the control situation than for 
conditions of PEM, mechanical ventilation with PEEP 20 cm HjO and use of NE. 
In these cases, values closer to 0 were observed with increasing p. In the radial 
direction (Figure 2C), the change in r s p a t signal with increasing ρ shows the 
dependence of relative perfusion for the epi-endocardial region of each sector in 
addition to the well-known global epi-endocardial perfusion gradient. After P20 
and NE, a trend toward zero, similar to the other directions, was observed. 
A rapid drop to 0 in r t with increasing ρ is the typical pattern of 
independence (strictly, no linear dependence) (7). Thus, the observations based 
on 3-dimensional autocorrelation function demonstrate that, under the experimen­
tal conditions used, there was some degree of neighborhood dependence of 
regional LV myocardial blood flow. Under conditions of PEM, mechanical 
ventilation with PEEP of 20 cm Kfi and use of NE, in addition to more 
homogeneous distribution of relative perfusion, there was a significant decrease 
of neighborhood dependence. 
References 
l.SestierFJ,MildenbergerRR&Klas^ 
2. Schanzenbacher Ρ & Klocke FJ (1980). Circulation, 61: 590-595. 3. Marcus ML, Kerber RE, 
Ehrhardt J & Abboud FM (1975). Circulation, 52:254-263.4. King RB, Bassingthwaighte JB, Hales 
JRS & Rowell LB (1985). Circulation Research,57:285-295.5. Austin Jr RE, Aldea OS, Coggins DL, 
Flynn AE & Hoffman JIE (1990). Circulation Research, 67:319-331.6. Zwissler B, Forst Η, Ishii Κ 
& Messmer Κ (1989). Research in Experimental Medicine, 189:427-438.7. Bendat JS & Piersol AO 
(1971). Random Data: Analysis and Measurement Procedures. Wiley- Interscience, New York, 18-
22,181-184,311-314.8. van BeekJHO, Roger SA&Bassingthwaighte JB (1989). Xmenca/iJowrna/ 
of Physiology, 257: H1670-H1680. 
Received April 10,1992 
Accepted November 19,1992 
Brazilian J Med Biol Res26(1) 1993 


Heterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine

Open Access LMU

Brazilian J Med Biol Res (1993) 26:37-42 ISSN0100-879X Short CommunicationHeterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine M.E Vidal~Melo\ R. Schosser2, CS. Barcelos1, B. Zwissler3 and K. Messmer3 1Programa de Engenharia Biomädica, COPPE, Universidade Federal do Rio de Janeiro, 21945-970 Rio de Janeiro, RJ, Brasil 2Abteilung fuer Experimentelle Chirurgie, Universitaet Heidelberg, W-6900 Heidelberg, Germany 3Institut fiier Chirurgische Forschung, Universitaet Muenchen, W-8000 Muenchen, Germany Regional left ventricular myocardial blood flow was studied in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure (PEEP)* The analysis was based on a 3-dimensional extension of the autocorrelation function used to assess the spatial correlation ( r ^ ) of myocardial perfusion. Experiments were performed on 8 premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 mg/kg) and glass beads. Successive PEEP values of 10, IS and 20 cm H^O (P20) were applied and norepinephrine (NE, 0.2-1.0 pg min"1 kg"1) was administered after P20. Regional perfusion was measured with radioactive microspheres. The left ventricle (LV) was dissected into 2S6 samples, was computed as the correlation of regional perfusions of samples ρ units apart in the apex-to-base, endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation (control, C) , P20 and NE. Control values of r ^ were around 50% in the apex-to-base and angular directions and the sign was inverted in the endo-epicardial direction. A reduction of r ^ to values close to zero was observed in all directions for P20 and NE. This is the typical pattern of independent distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree of neighborhood dependence of regional L V myocardial blood flow. This dependence is not observed under PEM, mechanical ventilation with PEEP and NE. Key words: autocorrelation, perfusion, left ventricle, microspheres, myocardial perfusion, blood flow heterogeneity. Presented at the VII Annual Meeting of the Federaf äo de Sociedades de Biologia Experimental, Caxambu, MG, August 26-29,1992. Correspondence: M.F. Vidal-Melo, Programa de Engenharia Biomedica, COPPE, Universidade Federal do Rio de Janeiro, Caixa Postal 68510,21945-970 Rio de Janeiro, RJ, Brasil. 38 Μ.F. Vtdal-Meloetal. The presence of myocardial blood flow heterogeneity (MBFH) under physiological and pathological conditions is an established concept. Several methods have been used to express this heterogeneity as statistical parameters (e.g., coefficient of variation (1)) or by graphic approaches (e.g., histograms (2,3) and density functions (4)). It has been shown that changes of MBFH occur under different pathophysiological conditions (1,2,5). It might be hypothesized that these changes are accompanied by changes of the 3-dimensional neighborhood dependences or spatial correlation of blood flow. However, none of the usual techniques for quantification of MBFH permits the study of this variable. In the present report we use an expanded concept of the autocorrelation function, a technique employed in signal processing, to analyze left ventricular myocardial blood flow in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure (PEEP) and pharmacologically treated with norepinephrine (NE). Experiments were performed on 8 foxhounds (18 ± 2 kg) premedicated with 1.5-2.0 ml propiomazine, anesthetized with 20 mg/kg pentobarbital sodium, 0.75 mg/kg piritramid and 0.25 mg/kg alcuronium iv and maintained by continuous infusion of pentobarbital (5 mg kg"1 h*1). Ringer solution was administered at a rate of 5 ml kg"1 h"1 throughout the experiment. The dogs were intubated and mechanically ventilated (FI0 2 s 100%, 12 cpm). Tidal volumes were adjusted to keep P e tC0 2 between 35 and 45 mmHg. After surgical preparation, the animals were isovolemically hemodiluted with 6% dextran 60 to a hematocrit of 28% and allowed to stabilize for 30 min, after which control measurements (C) were performed. Experimental PEM was produced with oleic acid (0.01 ml/kg) and glass beads (100 μιη diameter) as previously described (6). After at least 70 min of stabilization, PEEP was increased progressively to 10,15 and 20 cm H 2 0 (P20). Finally, norepinephrine (NE) was administered (0.2-1.0 pg kg"1 min"1) while PEEP was maintained at 20 cm I^O. Organ blood flow was measured with NEN-TRAC microspheres (diameter 16.5 ± 0.1 μπι) labeled with 141Ce, 5 1Cr, 1 0 3Ru, 1 1 4 In , 46Sc or 9 5Nb, injected into the left atrium (average of 40,000 particles/kg) within a period of 30 s. The arterial reference blood sample was drawn from the right femoral artery over 3 min at a rate of 3.24 ml/min. The regional myocardial blood flow was analyzed after C, P20 and NE. The dissection scheme for the left ventricle (LV) is shown in Figure 1. After fixing the heart in 6% formaldehyde for 1 week, the atria were removed and the heart was dissected into 10 slices perpendicular to its axis, beginning Brazilian J Med Biol Res 26(1) 1993 Regional ventricular myocardial bloodflow 39 Figure 1 - Dissection scheme of left ventricular myocardium. at the base. Slices 1-8 were subdivided into LV, right ventricle and septum. LV free wall and septum were considered to constitute the LV. Each LV slice was cut into 8 segments and further subdivided into 4 layers, resulting in 256 samples. Spatial correlation (r t) was determined on the basis of an extension of the digital autocorrelation function estimate (7) to the 3-dimensional case. As used in this study, it provides the correlation of the relative perfusion (RP) of samples ρ units apart. Thus, when ρ s 0, r t s 1. Correlations were computed with ρ varying in the endo-epicardial (r = 1,4, layers), angular (a = 1,8, sectors) and apex-to-base (h s 1,8, slices) directions. Brazilian J Med Biol Res 26(1) 1993 40 Μ. F. Vtdal-MeloetaL The r s p a t estimate for each displacement ρ in a given direction was computed as: •y direction rS p a t (p) = - 7 ; CD Vglobal where: rah w (2) R R . . -^rah j N f N , N h R P ' N ^ I l R P r a h (3) x ^ r=l a=l h=l Ν, N 8 N h V g i o b a ^ I I I ^ r a h - R P V r^l a5*! h«l (4) Ν , - ρ N , N h Vi = ^ 7 ± : Σ I I C R P r a h - R P K R P i r ^ a h - R P ) (5) L y t Ρ r-l a-lh-1 N , N , N h * Σ IXCRPrah " RPXRPra p h " (6) r-l a-1 h-1 N r N a N h - p V P H =ΤΤΤΣΣ Σ ^ - ^ Χ ^ ί Κ . ρ ) - ^ ) (7) i N h Ρ r-l a-1 h-1 Ν = total number of samples; N r = number of layers; N a = number of sectors; N h = number of slices; = blood flow measured in sample with coordinates rah; = weight of sample with coordinates rah; ap = a + ρ for (a + p)<Na; ap = a + ρ - N a for (a + p)>Na; V g l o b a l ä global variance of relative perfusion; V ,^ V* and ν£ β covariance of relative perfusions of samples ρ units apart in the directions r (layers), a (sectors) and h (slices), respectively. Brazilian J Med Biol Res 26(1) 1993 Regional ventricular myocardial bloodflow 41 The coefficients of variation of RP for the C, P20 and NE experimental points were 25.2 ± 5.2%, 20.5 ± 3.3% and 18.4 ± 3.8% (P<0.05 for pairwise comparisons). Plots of spatial correlation (r t) against ρ in angular direction are shown in Figure 2A for C, P20 and NE. Curves are symmetrical in relation to ρ = 4. Note that the NE curves fall to values closer to 0 than C curves as ρ increases. P20 assumes intermediate values. This reduction to 0 of P20 and mainly NE can also be observed in Figure 2B for the apex-to-base direction. Figure 2C shows plots of r ^ for radial direction. For ρ • 1 no distinction between C, P20 and NE is observed. At ρ - 2 and more clearly for ρ = 3 there is a separation between C values, which become negative, and P20 and NE values, which remain close to 0. -0.5 I ι ι , ι ι » • 0 1 2 3 4 5 6 7 P-Sector P-Laycr -0.5 I " « « " ·——' 0 1 2 3 4 5 6 7 P-Slice Figure 2 - Plots of the spatial autocorrelation function for control (circles), PEEP of 20 cm HjO (triangles) and norepinephrine (squares). Data are reported as means ± SD. A: Angular direction. Note the reduction to zero for NE; Β: apex-to-base direction. Note the faster re­duction to zero for NE followed by P20; C: endo-epicardial direction. Note that control values change sign and assume negative val­ues. This is related to the presence of a depen­dent endo-epicardial perfusion gradient. Curves for P20 and N E drop to values near zero. *P<0.05 for the test of equality of all three points at a given p; *P<0.05 for compari­son between C and NE (Friedman's test). Brazilian J Med Biol Res 26(1) 1993 42 M.F. Vidal-MeloetaL Recently, van Beek et al. (8) proposed a method for estimating spatial correlation using fractal dimension. Austin Jr. et al. (5) used auto-correlation in a 2-dimensional approach, without considering direction, to assess local conti­nuity. In the present study we present a method based on autocorrelation which considers direction and permits direct computation of the degree of 3-dimensional neighborhood dependence of LV myocardial perfusion. In the apex-to-base and angular directions, the results show higher correlations of relative perfusion among regions for the control situation than for conditions of PEM, mechanical ventilation with PEEP 20 cm HjO and use of NE. In these cases, values closer to 0 were observed with increasing p. In the radial direction (Figure 2C), the change in r s p a t signal with increasing ρ shows the dependence of relative perfusion for the epi-endocardial region of each sector in addition to the well-known global epi-endocardial perfusion gradient. After P20 and NE, a trend toward zero, similar to the other directions, was observed. A rapid drop to 0 in r t with increasing ρ is the typical pattern of independence (strictly, no linear dependence) (7). Thus, the observations based on 3-dimensional autocorrelation function demonstrate that, under the experimen­tal conditions used, there was some degree of neighborhood dependence of regional LV myocardial blood flow. Under conditions of PEM, mechanical ventilation with PEEP of 20 cm Kfi and use of NE, in addition to more homogeneous distribution of relative perfusion, there was a significant decrease of neighborhood dependence. References l.SestierFJ,MildenbergerRR&Klas^ 2. Schanzenbacher Ρ & Klocke FJ (1980). Circulation, 61: 590-595. 3. Marcus ML, Kerber RE, Ehrhardt J & Abboud FM (1975). Circulation, 52:254-263.4. King RB, Bassingthwaighte JB, Hales JRS & Rowell LB (1985). Circulation Research,57:285-295.5. Austin Jr RE, Aldea OS, Coggins DL, Flynn AE & Hoffman JIE (1990). Circulation Research, 67:319-331.6. Zwissler B, Forst Η, Ishii Κ & Messmer Κ (1989). Research in Experimental Medicine, 189:427-438.7. Bendat JS & Piersol AO (1971). Random Data: Analysis and Measurement Procedures. Wiley- Interscience, New York, 18-22,181-184,311-314.8. van BeekJHO, Roger SA&Bassingthwaighte JB (1989). Xmenca/iJowrna/ of Physiology, 257: H1670-H1680. Received April 10,1992 Accepted November 19,1992 Brazilian J Med Biol Res26(1) 1993 

Circulation Research,57:285-295.5. Austin Jr RE,

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Heterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine

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