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Vol. 83, Issue 6, 1832-1841, December 1997
1 Institute for Surgical Research and 2 Institute of Anesthesiology, University of Munich, 81366 Munich, Germany
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Kleen, Martin, Martin Welte, Peter Lackermeier, Oliver
Habler, Gregor Kemming, and Konrad Messmer. Myocardial blood flow
heterogeneity in shock and small-volume resuscitation in pigs with
coronary stenosis. J. Appl. Physiol.
83(6): 1832-1841, 1997.
We analyzed the effects of shock and
small-volume resuscitation in the presence of coronary stenosis on
fractal dimension (D) and spatial
correlation (SC) of regional myocardial perfusion. Hemorrhagic shock
was induced and maintained for 1 h. Pigs were resuscitated with
hypertonic saline-dextran 60 [HSDex, 10% of shed blood volume
(SBV)] or normal saline (NS; 80% of SBV). Therapy was continued
after 30 min with dextran (10% SBV). At baseline, D was 1.39 ± 0.06 (mean ± SE;
HSDex group) and 1.34 ± 0.04 (NS group). SC was 0.26 ± 0.07 (HSDex) and 0.26 ± 0.04 (NS). Left anterior descending coronary
artery stenosis changed neither D nor
SC. Shock significantly reduced D
(i.e., homogenized perfusion): 1.26 ± 0.06 (HSDex) and 1.23 ± 0.05 (NS). SC was increased: 0.41 ± 0.1 (HSDex) and 0.48 ± 0.07 (NS). Fluid therapy with HSDex further decreased
D to 1.22 ± 0.05, whereas NS did
not change D. SC was increased by both
HSDex (0.56 ± 0.1) and NS (0.53 ± 0.06). At 1 h after
resuscitation, SC was constant in both groups, and
D was reduced only in the NS group
(1.18 ± 0.02). We conclude that hemorrhagic shock homogenized
regional myocardial perfusion in coronary stenosis and that fluid
therapy failed to restore this.
fractals; spatial heterogeneity; regional perfusion; hypertonic
saline; dextran
INTRODUCTION IT IS NOW WELL RECOGNIZED that regional distribution of
myocardial blood flow is heterogeneous. Relative dispersion
(RD), a conventionally used measure of perfusion
heterogeneity, is dependent on the spatial resolution of the
measurement method. It increases when spatial resolution of the
measurement is increased. The comparison of data obtained in different
laboratories may therefore be misleading because uniform dissection
schemes for organs are precluded by animal size and technical
possibilities. This dilemma has been resolved by the introduction of
fractal analysis of myocardial blood flow heterogeneity (1, 31). With
fractal analysis, the increase of RD is set in relation to increasing
resolution. From this analysis, a single parameter, the fractal
dimension (D), may be calculated as
1 Correlation of perfusion in adjacent tissue samples has been suggested
as a method of assessing self-similarity of regional myocardial blood
flow (24, 26). The resulting correlation coefficients may vary from 0 to 1. Zero signifies that no linear relationship of blood flow to
neighboring tissue regions exists, whereas 1 indicates a deterministic
linear relationship of neighboring blood flow values.
Hypervolemic hemodilution causes a reduction of
D of perfusion in canine hearts from
1.17 to 1.09 (i.e., homogenizes perfusion). This has been attributed to
increased coronary blood flow (5). Reduction of coronary perfusion
pressure reduced local correlation of regional perfusion, whereas
pharmacological vasodilatation partly reversed this phenomenon (26).
These data indicate that alteration of hemodynamic determinants of
coronary perfusion may impair the physiological nonlinear regulation of
RMP. Coronary artery stenosis may reduce poststenotic perfusion
pressure and therefore aggravate shock-induced alterations. The high
prevalence of ischemic heart disease in surgical patients (21, 22)
suggests that the combination of silent ischemia and traumatic
hemorrhagic shock may be frequent and therefore warrants examination.
Myocardial ischemia induces disturbances of distribution of blood flow
(3, 14). Small-volume resuscitation has been shown to attenuate
microvascular disturbances in striated muscle after ischemia (27).
Capillary narrowing in hemorrhagic shock is reversed by infusion of
hypertonic solutions (25), and coronary vessels are dilated by infusion
of hypertonic saline (30). These data suggest that shock, particularly
when ischemia is aggravated by coronary stenosis, induces disruption of
the physiological regulation of blood-flow distribution. Infusion of
hypertonic/hyperoncotic solution may potentially reverse these changes
and restore physiological heterogeneity.
In this report, we present results of fractal analysis and spatial
correlation analysis of RMP data taken from a previously published
study on the effects of hypertonic saline-dextran (HSDex) resuscitation
on poststenotic myocardial perfusion (35). We hypothesized that
1) critical coronary stenosis alone
would not change heterogeneity because, by definition, perfusion is not compromised under resting conditions;
2) induction of shock would disrupt
the physiological pattern of blood flow distribution and therefore
change D and spatial correlation; and
3) therapy with hypertonic solution
would reverse these effects to some extent through its vascular
effects, whereas normal saline (NS) should be less active in this
respect.
METHODS
the slope of the linear relationship between the natural
logarithms of measurement resolution and perfusion heterogeneity
measured by RD. By using D, comparison
of data from different studies is possible and, at the same time,
proper credit is given to the fact that regional myocardial perfusion
(RMP) displays fractal properties. Fractal analysis is increasingly accepted to further elucidate physiology of myocardial blood flow in
experimental animals (5, 15, 24, 26). Absolute regional myocardial
blood flow can also be measured in humans, and heterogeneity of RMP is
recognized to be of relevance in coronary artery disease (4, 7).
Fractal analysis may be used for patient data for the same benefit as
in animal studies. For myocardial perfusion heterogeneity, as
determined with RD (SD/mean), D may
vary from 1.0 (uniform distribution) to 1.5 (random uncorrelated
variations) (1). By definition, D is a
global measure of heterogeneity.
1 · h1
pentobarbital sodium; 20 µg · kg1 · h1
fentanyl), mechanically ventilated (fraction of inspired
O2 = 0.5) pigs. Animal care and
use was in compliance with the National Research Council Guide
("Guide for the Care and Use of Laboratory Animals," 7th ed.,
Washington, DC: Natl. Acad. Sci. Press, 1996). During shock, the opioid
and barbiturate doses were reduced by 50%. The animals were
instrumented with a micromanometer (PC 370; Millar Instruments,
Houston, TX) to measure left ventricular pressure and with a
fluid-filled catheter for assessment of aortic pressures. Cardiac
output and left anterior descending coronary artery (LAD) flow were
measured with ultrasonic flow probes (14 and 2 mm; Transonic, Ithaca,
NY). For injection of microspheres, a catheter (5-Fr; Arrow, Reading, PA) was inserted into the left atrium after needle puncture and secured in place with a circular suture. Critical coronary
stenosis of the LAD was induced by micromanipulator-assisted narrowing
of a thin Teflon-coated copper wire sling distal to the coronary flow
probe. Absence of a hyperemic response after complete occlusion (10 s)
was used to verify the critical stenosis (10).
rm = Irm (art/Iart), where
rm is RMP (in ml/min), Irm is the intensity of
emitted radioactivity from the myocardial tissue sample,
art is the arterial reference sample flow (6.47 ml/min), and Iart is the intensity of emitted radioactivity from the
reference sample. Sample perfusion was referenced to weight before
analysis.
Data analysis.
D was calculated by assessing
heterogeneity of regional perfusion (RD, i.e., SD/mean) repeatedly
while decreasing the resolution of measurement by adding neighboring
tissue samples. D was then determined
as 1 the slope of the linear relation of RD and resolution on a
log-log plot (see Fig. 1) (1, 5, 15, 24,
26, 31, 33).
To this end, we developed a computer program in the programming language C++ (Watcom C/C++ compiler version 10; Powersoft, Concord, MA) and validated it with data sets of known heterogeneity or D. Individual samples were used as well as aggregates of neighboring tissue units comprising 2(2 · 1), 4 (2 · 2), 12 (2 · 2 · 3), 24 (2 · 2 · 3 · 2), and 48 (2 · 2 · 3 · 2 · 2) individual samples. For this purpose, the LV was conceptually thought of as cut open vertically from the base of the heart to the apex at the posterior border of the free wall and spread out as a flat plate. Looking at this plate from the endocardial side, we assigned coordinates in the x, y, and z directions, starting with x = 1, y = 1, and z = 1. The upper left and innermost point, i.e., the endocardial side of the LV where it joins the septum at the base of the heart, was defined as having coordinates x = 1, y = 1, and z = 1. Coordinates were assigned, with z representing the transmural direction, x representing the circumferential position, and y as the vertical direction from the base to the apex. Alternating between x, y, and z directions and starting with the x direction, the algorithm was designed to repetitively average perfusion of either two or three adjacent tissue samples (or tissue sample aggregates). In the computer algorithm, the decision of whether to use two or three samples was generalized, and the choice depended on whether division of the number of remaining sample aggregates by two or by three yielded an integer result. In the present experiments, three aggregate samples were averaged only in the third recombination step. To examine the impact of different modes of recombination of samples and sample aggregates, we recalculated D by using aggregates of whole circumferential sectors of myocardium. For this purpose, the recombination algorithm was modified to perform recombinations only within circumferential sectors. In 1992, Glenny (8) proposed spatial correlation of regional pulmonary blood flow as a new parameter for characterizing distribution of regional perfusion. Correlation of flow to adjacent myocardial regions has subsequently been used as a method of assessing self-similarity of regional myocardial blood flow in addition to the global D (24, 26). For calculation of spatial correlation, all blood flow values from adjacent tissue samples are treated as data pairs and are used as variables for a three-dimensional extension of the standard correlation formula as reported by Glenny (8). We implemented this formula with a computer program written in C++ (Watcom C/C++ compiler version 10; Powersoft). Bassingthwaighte et al. (2) have pointed out that spatial correlation and D are linked by the formula r = 23
2D 1, where
r is spatial correlation. By
rearranging, D = {log2[23/ (r + 1)]}/2 is obtained. We calculated the
D from
r by using the latter formula and
compared results with both direct determination of
D and calculation with
r.
Statistics.
All statistical analyses were performed by using SAS version 6.1 (SAS
Institute, Cary, NC). After verification of normal distribution of data
with the Shapiro Wilks test, analysis of variance for repeated
measurements was used to test the presence of global differences.
Duncan's multiple-range test was performed on significant F-values. The type 1 error level was
set to 5%. All data are presented as means ± SE.
RESULTS
Oxygenation parameters, acid-base status, and regional myocardial metabolism and function have been described in detail previously (35). A summary of central hemodynamic and regional myocardial blood flow data is given in Table 1. Heart rate increased with shock and was reduced by infusion therapy in both groups. There was a difference in MAP between groups at baseline but not after LAD stenosis induction. Neither therapy increased MAP significantly, whereas cardiac index was enhanced in both groups after significant reduction during shock. Cardiac index remained at this level until the end of the protocol in both groups. LV end-diastolic pressure (LVEDP) reduction indicated hypovolemia in both groups. LVEDP was corrected immediately only in the HSDex group, whereas LVEDP increased in the NS group only after the second part of resuscitation. The subendocardial-to-subepicardial blood flow ratio (EER) was lowered by LAD stenosis only in the NS group but was still >1, excluding significant subendocardial ischemia. In both groups, shock reduced EER to <1, and EER was not improved by resuscitation. In the NS group, EER was further decreased after 1 h. Subendocardial blood flow in the NS group was higher than in the HSDex group before therapy. Whereas HSDex infusion significantly increased subendocardial blood flow from a very low level up to baseline values, NS induced no significant increase in the innermost myocardial layer. However, perfusion was as high as in the HSDex group 1 h after primary resuscitation. In the subepicardial myocardium, neither stenosis nor shock nor fluid therapy induced significant changes. In both groups, at 1 h after first volume therapy, there was a large increase in subepicardial perfusion.
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Induction of the LAD stenosis did not affect the
D in either group (Table
2). Hemorrhagic shock reduced
D, i.e., homogenized perfusion,
significantly by 9 (HSDex) and 7% (NS) in both groups. These decreases correspond to 26 and 18% of the theoretical total possible range of D (1.0-1.5;
Ref. 1). At 5 min after resuscitation with HSDex, LV blood flow was
further homogenized. After additional dextran infusion, there was a
trend toward further reduction, but this was without statistical
significance. Therapy with NS after 5 min did not elicit the same
effect as HSDex. However, after 1 h, D
was significantly reduced, and a status was reached equivalent to that
in the HSDex group. Single plots of the natural logarithms of RD and sample size are shown in Figs. 1 and
2. Data points fitted linear-regression
equations exceptionally well, as evidenced by the correlation
coefficients (mean ± SE: baseline, 0.94 ± 0.02;
stenosis, 0.95 ± 0.01; shock, 0.96 ± 0.01;
R5, 0.96 ± 0.01;
R60, 0.96 ± 0.01). The
D values are given by the difference
between 1 and the slope of the respective line.
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Blood flow to subendocardial myocardial tissue samples was significantly more homogeneous than blood flow to subepicardial myocardium, as evidenced by lower D values in both groups (Table 2). This difference persisted throughout the experiment. Neither stenosis nor shock nor resuscitation altered subepicardial D in the HSDex group, whereas shock in the NS group induced a 5% reduction of D, which was not influenced thereafter. Stenosis did not affect subendocardial D in the HSDex group, but stenosis significantly reduced subendocardial D in the NS group (10%). Shock homogenized subendocardial D in both groups by 20 (HSDex) and 9% (NS). Infusion of neither resuscitation fluid changed D in the innermost layer of the myocardium.
D values that were calculated from r did not differ from values derived from analysis of RD (values for complete LV). Analysis of variance for differences within either group showed insignificant differences (P = 0.32 and P = 0.63, respectively) as did the tests for differences between group at each time point (P = 0.48, 0.38, 0.45, 0.74, and 0.74). The mean difference of both values for D was 0.0005 ± 0.01.
When comparing D values that were calculated by using aggregates of whole circumferential sectors with D values that were calculated from recombining the whole LV, there were no statistically significant differences. There was a mean difference of 0.006 ± 0.008 between both values.
Results for spatial correlation (self-similarity) of flows to adjacent myocardial tissue samples confirmed the results from fractal analysis. Shock significantly increased self-similarity of blood flow in both groups (Table 3). Resuscitation with both HSDex and NS (R5) further augmented flow homogeneity, and spatial correlation values had increased by 115 and 104% of baseline values in HSDex and NS, respectively.
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In contrast with D, spatial correlation values of subendocardial and subepicardial myocardial tissue perfusion were not different at any point in the protocol (Table 3). Critical stenosis of the LAD induced homogenization within the subepicardial layer in the HSDex group and within the subendocardial layer of the myocardium in NS group. Shock evoked stronger correlation of flow to neighboring regions, except within the subepicardial layer of the HSDex group. Resuscitation induced nonuniform changes. However, 1 h after infusion of HSDex and NS, spatial correlation values had increased by 157 and 65% compared with baseline in the subepicardial layers of the myocardium. In the subendocardial layers, correlation value had increased by 200 and 136% compared with baseline values.
In contrast with D and spatial correlation, RD as the conventional parameter of heterogeneity indicated more heterogeneous RMP in both groups during shock as well as after resuscitation in the NS group (Table 4). Coronary stenosis did not affect RD, but after induction of shock, there was a 68% increase of RD in the HSDex group and a 47% rise in the NS group. Infusion of NS further increased RD by 22%.
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Separate calculation of subendocardial and subepicardial RD revealed no change in the subepicardium in the HSDex group but significantly more heterogeneous perfusion in this layer in the NS group on both shock and resuscitation (Table 4). The subendocardial myocardium in both groups displayed increase of RD after induction of hypotension and augmentation of this effect with infusion of either solution. In the HSDex group, RD of subendocardial myocardial perfusion was lower (more homogeneous) than RD of subepicardial perfusion at baseline and was higher (more heterogeneous) at 5 min and 1 h after resuscitation.
DISCUSSION
Fractal geometry has been termed a design principle for living organisms (33). The universal nature of fractal trees in biology has recently been demonstrated by West et al. (36). The authors showed that modeling a wide variety of physiological processes (including nutritive perfusion) for different species of greatly different sizes was only successful if fractal tree models were used. Fractal properties of spatial variability of regional myocardial blood flow are now well established (1, 15, 31). However, nothing is known about the impact of shock or coronary stenosis or a combination of both on fractal properties of perfusion of the heart. It is also not known whether fluid therapy, which is known to restore to the original state alterations of blood flow that are induced by shock (19), can exert effects on D of myocardial perfusion.
Regional myocardial blood flow measurements have become possible in humans with the introduction of new techniques, such as positron emission tomography. Heterogeneity of perfusion is recognized to be of major relevance in coronary artery disease (7). Therefore, heterogeneity of flow and fractal analysis of cardiac perfusion have been deemed to have major implications for the measurement of flows in the myocardium of patients (4).
For example, in the past, fractal geometry of heart rate variability (29), retinal vascular branching pattern (20), and radiological tumor appearance (32) have successfully been used to diagnose human pathology. The lack of experimental data relating to D of RMP in the presence of coronary pathology is serious when one considers the possible relevance of this parameter for patients in the near future.
Myocardial ischemia induces changes in the microvascular network that interfere with normal distribution of blood flow (3, 14). Small-volume resuscitation has been shown to enhance nutritional flow (19) and to partially reverse leukocyte adhesion and extravasation in striated muscle vasculature after ischemia (27). Capillary narrowing in hemorrhagic shock is reversed by infusion of hypertonic solutions (25), and coronary vasodilation is induced by coronary infusion of hypertonic saline (30).
If distribution of perfusion is disturbed by ischemia, this should result in noticeable changes of heterogeneity parameters of regional myocardial blood flow. Coronary stenosis should, through aggravation of ischemia, increase changes induced by hemorrhagic shock. On the other hand, infusion of hypertonic solutions has been reported to reverse some of the untoward effects of ischemia on perfusion (19, 25, 27). The purpose of this study was to challenge these theoretical considerations and to test whether previous findings can be corroborated with new methods of heterogeneity analysis of regional blood flow.
To the authors' knowledge, the present report is the first on D and spatial correlation of regional myocardial blood flow in the presence of critical coronary stenosis and hemorrhagic shock.
Induction of critical LAD stenosis did not alter regional myocardial O2 delivery, lactate metabolism, regional perfusion, and regional myocardial function distal to the vascular stenosis (see Ref. 35 for detailed data). Poststenotic myocardial O2 delivery was reduced to 46 (NS) and 37% (HSDex) during shock. Blood flow to nonpoststenotic myocardium was maintained during shock. Conversely, in the poststenotic area, a significant reduction to 63 (NS) and 43% (HSDex) of preshock values took place. In both groups, the poststenotic myocardium produced lactate during shock. This effect was reversed in some animals when they were infused with HSDex, and the effect persisted in all NS-treated animals. These data show that significant ischemia was present during shock in the poststenotic myocardium.
Baseline D of the whole LV are in the range of what has been previously reported for dogs (15) but are slightly higher than data for baboons, sheep, and rabbits (1). Values of spatial correlation of LV perfusion at baseline were in the range that has been found previously (24). Taking into account the dependence of RD on sample mass, there was no difference between baseline values in the present study compared with those in previous reports (1, 15, 23).
As expected, heterogeneity parameters for the whole LV revealed minimal or no influence of critical LAD stenosis on regional blood flow. Shock, however, induced substantial reduction of D and increase of spatial correlation; both results indicate homogenization of flow distribution. In contrast, RD increased, demonstrating more heterogeneous distribution of local perfusion. A similar discrepancy between spatial correlation and RD has been observed for canine pulmonary perfusion after change of posture of the animals (9).
The physiological pattern of distribution of myocardial perfusion seems to be heterogeneity. Because, for example, subendocardial and subepicardial perfusion are known to be different in magnitude, this concept should be easy to accept. It has been shown in dogs that large spatial differences in myocardial perfusion are linked to proportional differences in local glucose metabolism. Differences in blood flow are not associated with differences in oxygenation; i.e., low-flow areas are not at risk for hypoxia (28). It can be concluded that perfusion heterogeneity is a necessary adaptation to local substrate needs. Heterogeneity of RMP has been shown to be a stable phenomenon over time (17). Heterogeneity of RMP was demonstrated to be stable over hours before and after sympathetic stimulation (6).
Homogenization during shock may therefore be interpreted as either an expression of detrimental effects of shock or as an adaptive response of the myocardium. In either case, reversal of induced reductions of heterogeneity may be seen as beneficial. Such reversal would either show that adaptations are not necessary anymore or that shock effects are no longer operative. However, therapy of hemorrhagic shock did not reverse reductions of D but aggravated reductions of D in the HSDex group. Increases of spatial correlations in both groups and increases of RD in the NS group were also augmented by fluid resuscitation from shock.
Approximated RD of regional myocardial blood flow (calculated by dividing reported SD by average blood flow) from previous studies shows that the increase of RD on induction of hemorrhagic shock is a common finding (13, 23).
This paradoxical result of opposing findings for heterogeneity as indicated by RD, D, and spatial correlation stresses the importance of calculation of different parameters during analyses of heterogeneity. Whereas RD averages global perfusion, spatial correlation averages the local mutual relationship of neighboring tissue samples. D, however, measures the change of heterogeneity with changing aggregate sample size. Whereas D is based on information from the whole fractal plot (Fig. 1), RD may be considered to represent only the intercept of such a plot. The slope of a fractal plot, and thus D, may well increase or decrease while the intercept at the same time remains unchanged or decreases or increases. The effects of any form of intervention on D, spatial correlation, and simple RD of myocardial perfusion have never before been compared.
The present report is the first to present separate calculations of D for subendocardial and subepicardial myocardium. This analysis yielded values for subepicardial but not for subendocardial samples that are slightly above the D that is expected for completely uncorrelated regional flow values (i.e., 1.5) (1). However, it has been pointed out that under special circumstances, when inverse correlations of regional myocardial flow become evident, a D of >1.5 is possible (1, 2). We interpret those values as indicating very heterogeneous, non-self-similar perfusion in the subepicardial myocardium. Biological or statistical noise may have caused D to be above the theoretical limit of 1.5. On the other hand, for the subepicardial myocardium, the mathematical relationship of spatial correlation and D did not follow the equation formulated by Bassingthwaighte et al. (2). However, in the case of subendocardial myocardium, the data did fit the equation. This might raise the question whether the methodology failed because of low sample numbers, for instance. However, close examination of the blood flow results and of results from fractal analysis gave no indication of methodological flaws.
Homogeneity of regional blood flow when analyzed for all transmural layers together but random perfusion of separated tissue layers at baseline may be explained by the coupling of subendocardial and subepicardial perfusion. The ratio of perfusion to neighboring epicardial and endocardial regions is uniformly reported to be tightly regulated (3, 13, 16). Separating regions of coupled perfusion resulted in increased D but not in increased RD or spatial correlation.
It is striking that in both groups D values derived from subepicardial myocardium varied minimally, whereas subendocardial D decreased dramatically on induction of shock and remained depressed despite shock therapy.
In contrast to global, sample size-independent heterogeneity (D), spatial correlation did not display this difference between myocardial tissue layers. Shock increased spatial correlation, and therapy augmented this result in part. RD of separated LV wall layers partially confirmed the findings for D. In the HSDex group, RD of the epicardial tissue layer did not change in response to shock and therapy, whereas the endocardial layer displayed dramatically increased RD. In the NS group, this pattern was not as marked. We conclude that shock in the presence of critical coronary stenosis affects most pronouncedly subendocardial perfusion heterogeneity. This may be due to mechanisms operational during shock that preferentially change blood flow distribution within subendocardial tissue portions. Subendocardial edema and consecutive compression of intramyocardial vessels (3), as well preferential swelling of myocytes in the subendocardium (14), might induce heterogeneous distribution of perfusion during ischemia and thus explain the observed differences.
In conclusion, we have provided the first experimental data on D and spatial correlation for myocardial perfusion in the presence of critical coronary stenosis and shock. Separation of subendocardial and subepicardial tissue portions revealed that global homogeneity measured with D of myocardial perfusion may be due to local transmural coupling of blood flow, because separation of transmural layers resulted in random distribution of flow. Separate calculations, similar to the present study, for transmural myocardial layers have never before been published.
Previous reports suggested that small-volume resuscitation reverses many of the untoward effects of ischemia in the microcirculation. Our results do not support the assumption that these beneficial effects exert a significant influence on distribution of myocardial perfusion. Neither HSDex nor NS fluid resuscitation elicited reversal of shock-induced reduction of D or reversal of increased spatial correlation. Fluid infusion aggravated changes in part. However, it is important to emphasize the difference between previous reports and the present study because no coronary stenosis was present in previous studies. The lack of efficacy of small-volume resuscitation in terms of restoration of perfusion heterogeneity in our model may be interpreted as the result of impaired distribution of myocardial blood flow after shock in the presence of coronary stenosis that could not be reversed.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the valuable contribution of Leandra Kuhn to experimentation and data acquisition as well as the professional care for the animals by the team of Otto Frisch.
FOOTNOTES
Address for reprint requests: M. Kleen, Institute for Surgical Research, Univ. of Munich, Marchioninistr. 15, 81366 Munich, Germany (E-mail: kleen{at}icf.med.uni-muenchen.de).
Received 24 March 1997; accepted in final form 25 July 1997.
REFERENCES
| 1. |
Bassingthwaighte, J. B.,
R. B. King,
and
S. A. Roger.
Fractal nature of regional myocardial blood flow heterogeneity.
Circ. Res.
65:
578-590,
1989 |
| 2. | Bassingthwaighte, J. B., J. H. G. M. Van Beek, and R. B. King. Fractal branchings: the basis of myocardial flow heterogeneities. Ann. NY Acad. Sci. 591: 392-401, 1990[Medline]. |
| 3. | Carlson, E. L., S. L. Selinger, J. Utley, and J. I. E. Hoffman. Intramyocardial distribution of blood flow in hemorrhagic shock in anesthetized dogs. Am. J. Physiol. 230: 41-49, 1976. |
| 4. |
Chilian, W. M.
Coronary microcirculation in health and disease.
Circulation
95:
522-528,
1997 |
| 5. |
Cousineau, D. F.,
C. A. Gorensky,
J. R. Rouleau,
and
C. P. Rose.
Microsphere and dilution measurements of flow and interstitial space in dog heart.
J. Appl. Physiol.
77:
113-120,
1994 |
| 6. | Deussen, A., C. W. Flesche, T. Lauer, M. Sonntag, and J. Schrader. Spatial heterogeneity of blood flow in the dog heart. II. Temporal stability in response to adrenergic stimulation. Pflügers Arch. 432: 451-461, 1996[Medline]. |
| 7. | Gewirtz, H., H. A. Skopicki, S. A. Abraham, H. Castano, R. E. Dinsmore, N. M. Alpert, and A. J. Fischman. Quantitative PET measurements of regional myocardial blood flow: observations in humans with ischemic heart disease. Cardiology 88: 62-70, 1997[Medline]. |
| 8. |
Glenny, R. W.
Spatial correlation of regional pulmonary perfusion.
J. Appl. Physiol.
72:
2378-2386,
1992 |
| 9. |
Glenny, R. W.,
N. L. Polissar,
S. McKinney,
and
H. T. Robertson.
Temporal heterogeneity of regional pulmonary perfusion is spatially clustered.
J. Appl. Physiol.
79:
986-1001,
1995 |
| 10. | Gould, K. L., K. Lipscomb, and G. W. Hamilton. Physiologic basis for assessing critical coronary stenosis. Am. J. Cardiol. 33: 87-94, 1974[Medline]. |
| 11. | Gross, W., R. Schosser, and K. Messmer. MIC-III: an integrated software package to support experiments using the radioactive microsphere technique. Comput. Programs Biomed. 33: 65-85, 1990. |
| 12. | Heymann, M. A., B. D. Payne, J. I. E. Hofmann, and A. M. Rudolph. Blood flow measurements with radionuclide-labeled particles. Prog. Cardiovasc. Dis. 20: 55-79, 1977[Medline]. |
| 13. | Horton, J. W., and D. S. Poehlmann. Regional coronary blood flow in canine hemorrhagic shock. Circ. Shock 23: 271-283, 1987[Medline]. |
| 14. |
Horton, J. W.
Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs.
Am. J. Physiol.
252 ((Heart Circ. Physiol. 21):
H1203-H1210,
1987 |
| 15. |
Iversen, P. O.,
and
G. Nicolaysen.
Fractals describe blood flow heterogeneity within skeletal muscle and within myocardium.
Am. J. Physiol.
268 ((Heart Circ. Physiol. 37):
H112-H116,
1995 |
| 16. | Kien, N. D., J. A. Reitan, D. A. White, C.-H. Wuh, and J. H. Eisele. Cardiac contractility and blood flow distribution following resuscitation with 7.5% hypertonic saline in anesthetized dogs. Circ. Shock 35: 109-116, 1991[Medline]. |
| 17. | King, R. B., and J. B. Bassingthwaighte. Temporal fluctuations in regional myocardial flows. Pflügers Arch. 413: 336-342, 1989[Medline]. |
| 18. | Kleen, M., O. Habler, and K. Messmer. A tool for balancing activity from isotopes used for the radioactive microsphere method. Comput. Methods Programs Biomed. 53: 81-86, 1997[Medline]. |
| 19. | Kreimeier, U., U. B. Brückner, S. Niemczyk, and K. Messmer. Hyperosmotic saline dextran for resuscitation from traumatic-hemorrhagic hypotension: effect on regional blood flow. Circ. Shock 32: 83-99, 1990[Medline]. |
| 20. |
Landini, G.,
P. I. Murray,
and
G. P. Misson.
Local connected fractal dimensions and lacunarity analyses of 60 degrees fluorescein angiograms.
Invest. Ophthalmol. Vis. Sci.
36:
2749-2755,
1995 |
| 21. | Mangano, D. T., M. Hollenberg, G. Fegert, L. Meyer, M. J. London, J. F. Tubau, and W. C. Krupski. Perioperative myocardial ischemia in patients undergoing noncardiac surgery. I. Incidence and severity during the 4 day perioperative period. J. Am. Coll. Cardiol. 17: 843-850, 1991[Abstract]. |
| 22. | Mangano, D. T., M. G. Wong, M. J. London, J. F. Tubau, and J. A. Rapp. Perioperative myocardial ischemia in patients undergoing noncardiac surgery. II. Incidence and severity during the 1st week after surgery. J. Am. Coll. Cardiol. 17: 851-857, 1991[Abstract]. |
| 23. | Maningas, P. A. Resuscitation with 7.5% NaCl in 6% dextran-70 during hemorrhagic shock in swine: effects on organ blood flow. Crit. Care Med. 15: 1121-1126, 1987[Medline]. |
| 24. |
Matsumoto, T.,
M. Goto,
H. Tachibana,
Y. Ogasawara,
K. Tsujioka,
and
F. Kajiya.
Microheterogeneity of myocardial blood flow in rabbit hearts during normoxic and hypoxic states.
Am. J. Physiol.
270 ((Heart Circ. Physiol. 39):
H435-H441,
1996 |
| 25. | Mazzoni, M. C., P. Borgström, M. Intaglietta, and K. E. Arfors. Capillary narrowing in hemorrhagic shock is rectified by hyperosmotic saline-dextran reinfusion. Circ. Shock 31: 407-418, 1990[Medline]. |
| 26. |
Mori, H.,
M. Chujo,
S. Haruyama,
H. Sakamoto,
Y. Shinozaki,
M. Uddin-Mohammed,
A. Iida,
and
H. Nakazawa.
Local continuity of myocardial blood flow studied by monochromatic synchrotron radiation-excited X-ray fluorescence spectrometry.
Circ. Res.
76:
1088-1100,
1995 |
| 27. |
Nolte, D.,
M. Bayer,
H.-A. Lehr,
M. Becker,
F. Krombach,
U. Kreimeier,
and
K. Messmer.
Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran.
Am. J. Physiol.
263 ((Heart Circ. Physiol. 32):
H1411-H1416,
1992 |
| 28. | Sonntag, M., A. Deussen, J. Schultz, R. Loncar, W. Hort, and J. Schrader. Spatial heterogeneity of blood flow in the dog heart. I. Glucose uptake, free adenosine and oxidative/glyocolytic enzyme activity. Pflügers Arch. 432: 439-450, 1996[Medline]. |
| 29. | Turcott, R. G., and M. C. Teich. Fractal character of the electrocardiogram: distinguishing heart-failure and normal patients. Ann. Biomed. Eng. 24: 269-293, 1996[Medline]. |
| 30. | Vacca, G., B. Papillo, A. Battaglia, E. Grossini, D. A. S. G. Mary, and G. Pelosi. The effects of hypertonic saline solution on coronary blood flow in anaesthetized pigs. J. Physiol. (Lond.) 491: 843-851, 1996[Medline]. |
| 31. |
Van Beek, J. H. G. M.,
S. A. Roger,
and
J. B. Bassingthwaighte.
Regional myocardial flow heterogeneity explained with fractal networks.
Am. J. Physiol.
257 ((Heart Circ. Physiol. 26):
H1670-H1680,
1989 |
| 32. | Velanovich, V. Fractal analysis of mammographic lesions: a feasibility study quantifying the difference between benign and malignant masses. Am. J. Med. Sci. 311: 211-214, 1996[Medline]. |
| 33. |
Weibel, E. R.
Fractal geometry: a design principle for living organisms.
Am. J. Physiol.
261 ((Lung Cell. Mol. Physiol. 5):
L361-L369,
1991 |
| 34. | Welte, M., T. Goresch, L. Frey, K. Holzer, B. Zwissler, and K. Messmer. Hypertonic saline dextran does not increase cardiac contractile function during small volume resuscitation from hemorrhagic shock in anesthetized pigs. Anesth. Analg. 80: 1099-1107, 1995[Abstract]. |
| 35. | Welte, M., P. Lackermeier, O. Habler, M. Kleen, G. Kemming, L. Frey, B. Zwissler, and K. Messmer. Effect of hypertonic saline/dextran on post-stenotic myocardial perfusion, metabolism, and function during resuscitation from hemorrhagic shock in anesthetized pigs. Shock 7: 119-130, 1997[Medline]. |
| 36. |
West, G. B.,
J. H. Brown,
and
B. J. Enquist.
A general model for the origin of allometric scaling laws in biology.
Science
276:
122-126,
1997 |
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