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Am J Physiol Heart Circ Physiol 281: H1913-H1918, 2001;
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Vol. 281, Issue 5, H1913-H1918, November 2001

Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 µm

J. Pieter Versluis, Johannes W. Heslinga, Pieter Sipkema, and Nico Westerhof

Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Pressure-flow relationships at the entrance of the coronary circulation in the diastolic myocardium exhibit a zero-flow pressure intercept (Pint). We tested whether this intercept is the same throughout the vascular bed. Microvascular pressure-flow relationships were therefore measured in vessels of various sizes of the maximally dilated vasculature of perfused unstimulated papillary muscle using the servo-null technique. From these relationships, Pint were calculated with nonlinear regression. The Pint at the level of the septal artery (diameter, 150-250 µm) was 23.2 ± 4.4 cmH2O (n = 12). In arterioles with a diameter range between 24 and 110 µm, Pint was 1.7 ± 0.5 cmH2O (n = 6, P < 0.01), significantly lower than in the septal artery but significantly higher than zero, and not dependent on vessel size. In venules with the same diameters, Pint was 1.1 ± 1.1 cmH2O (n = 4), which was not different from zero. We conclude that, in the dilated vascular bed of the papillary muscle, two vascular waterfalls are found. The first waterfall is located in arterioles between 150 and 110 µm. The second waterfall is probably located in the small postcapillary venules.

rat; servo-null; FITC-dextran; coronary flow; microvasculature


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

THE CORONARY PRESSURE-FLOW RELATIONSHIP in diastole exhibits an intercept with the pressure axis, the so-called zero-flow pressure intercept (Pint) (6). This Pint is present in blood-perfused and crystalloid-perfused hearts (22). The level of the intercept depends on the vasoactive state of the vascular bed (4) and is present even with maximal vasodilatation (13). A Pint higher than venous pressure implies that the effective perfusion pressure is decreased, i.e., with a higher Pint, a higher perfusion pressure is needed to generate the same flow. Pint might be caused by a waterfall mechanism (6) or an intramyocardial compliance (19). Most studies report pressure-flow relationships at the entrance of the coronary vasculature. These data give a pressure intercept for the entire vasculature (12) so that it is not possible to decide where the waterfall is located. Recently, Kanatsuka et al. (11) measured local flow in the subepicardium and related this to aortic pressure. However, relations between local flow and local pressure in the microvasculature, which could give the localization of Pint conclusively, have not been reported to date.

A vascular waterfall is independent of venous pressure until it exceeds the intercept pressure. By increasing venous pressure, two subsequent intercepts can be found in isolated skeletal muscle (5). However, in isolated hearts and perfused papillary muscles, it is impossible to control venous pressure due to Thebesian outflow. Therefore, only measurements of pressure in smaller vessels along the vasculature can elucidate the location of vascular waterfalls in the myocardium.

In the present study, we measured pressure-flow relationships in perfused diastolic papillary muscle. We measured pressure at the entrance (septal artery) and at the microvascular level using the servo-null technique (23), applying a range of perfusion pressures. In this way, we could obtain Pint in several sizes of vessels of the vasculature and find the location of the waterfall.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Experimental setup. All animals were treated in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (National Research Council, Washington, DC, 1996) as approved by the Council of the American Physiological Society and under the regulations of the Institutional Animal Care and Use Committee. Male Wistar rats (Harlan; Zeist, the Netherlands) weighing 275-300 g were used in all experiments (n = 12). Papillary muscles were obtained as previously described (16). The muscle was placed in an organ bath with a standard Tyrode solution containing (in mM) 128.3 NaCl, 4.7 KCl, 1.05 MgCl2, 0.42 NaH2PO4, 1.0 CaCl2, 11.1 glucose, and 20.2 NaHCO3. This solution was equilibrated by gassing continuously with 95% O2-5% CO2 (pH 7.4) and kept at a temperature of 27°C. When adenosine (0.1 mM) was added to the superfusion and perfusion fluid, no further increase in flow could be found, indicating maximal vasodilatation.

The organ bath was part of the experimental setup, as shown in Fig. 1. A silk thread was tied to the tendon and attached to a force transducer (AE801, Mikro-Elektronikk; Horten, Norway). The septal artery was then cannulated. The cannula was attached to a reservoir with Tyrode solution via a glass capillary (resistance). Changing the O2-CO2 pressure above the Tyrode solution alters the perfusion pressure. Perfusion pressure could be a constant value or a continuous increase in pressure ("ramp pressure," see Pressure-flow relationships). The pressure drop across the resistance capillary was measured with two combined pressure difference meters (type LX160ID, National Semiconductor; Santa Clara, CA). The flow through the resistance was found to be proportional to the pressure drop over the glass capillary (16).


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  		Fig. 1.   Schematic drawing of the experimental setup for intravascular pressure measurements. Note that the muscle is suspended in a muscle bath. For further details, see text. Pperf, perfusion pressure; Pinput, input pressure of the muscle; Delta P, pressure difference.

In each experiment, the flow through the system, before attachment to the muscle, was measured using a pressure step protocol. In this way, the perfusion pressure could be corrected for the pressure drop over the capillary and the pressure at the tip of the cannula was determined. This pressure at the level of the septal artery was considered to be the input pressure of the muscle (Pinput). Pinput was also measured in one experiment to show that the calculations were accurate. In this experiment, the slope between the calculated Pinput and measured septal artery pressure was 1.01 (r2 = 0.99), which was not different from 1. Thus in all experiments Pinput-flow relationships were determined in diastolic (not electrically stimulated) muscles at 80% of the maximum length (Lmax).

Microvascular pressure. Because the muscles were perfused with Tyrode solution, microvessels were not visible. With fluorescent-labeled large molecules, microvessels can be visualized without the risk of diffusion of the fluorescence through the interstitial space. Therefore, FITC-dextran (4 mg/ml, mol wt 150,000, Sigma; Bornem, Belgium) was added to the perfusate to visualize the vasculature. We used a modified halogen light source (KL 1500, Schott) with a 450- to 490-nm band-pass filter (Zeiss; Weesp, The Netherlands) to excite the FITC-dextran. The emitted light was visualized using a modified dissection microscope (SV 11, Zeiss) with 520-nm high-pass filters (Zeiss) in front of the oculars. In this way, vessels with a diameter >20 µm were visible.

Microvascular pressure (Pmv) was measured using a servo-null pressure system (model 5A, Instrumentation for Physiology and Medicine; San Diego, CA) based on the original technique used by Wiederhielm et al. (23). We used relative large pipettes (diameter >1 µm) (7) that are very sensitive to changes in pressure but not sensitive to plugging. Details of the technique used were described before by Heslinga et al. (9, 10). Micropipettes were pulled in a two-step protocol using a micropipette puller (BB-CH, Mecanex SA; Geneva, Switzerland). The tip diameter (outer diameter) of the pipettes was typically 2-5 µm, whereas the length of the tip was ~200 µm. The pipettes were filled with a 2 M NaCl solution. The pipette was mounted on an oil-driven micromanipulator (MM0-203, Narishige; Tokyo, Japan), allowing precise movements in three dimensions.

The validity of the recorded pressure was tested in three ways. 1) Once in the lumen of a vessel, the servo-null system should not change the mean pressure recorded when its gain is increased. An increase in gain of the servo-null system only induced high-frequency oscillations around the mean pressure. If the pipette was clogged or pressed against the wall of the vessel, an increase in gain would lead to an increase in recorded pressure. 2) Pipettes were filled with 1% carbon black solution. While applying counter pressure on the pipette, a small volume of carbon black solution was released in the vessel if the pipette was inserted in the vasculature. The black solution would then move with the flow along the vessel lumen. In the interstitial space, injection with carbon black would lead to a diffuse spot of ink in the muscle. In this way, we could also distinguish between arterioles and venules by evaluating the direction of the flow. Flow toward the tendon of the muscle was considered to be arteriolar and that toward the base was considered to be venular. This was confirmed by the pressure drop between Pinput and Pmv, which was higher in venules compared with arterioles. 3) A step in perfusion pressure should lead to an almost simultaneous step (response time <100 ms) in Pmv (10). In the case that the pipette was positioned in the interstitial space, a long response time (2 s) is found.

Pressure-flow relationships. Perfusion pressure in the supplying septal artery (Pinput) was changed from 15-100 cmH2O using a ramp pressure protocol. The perfusion pressure was changed by using a 20-ml syringe coupled to an injector (model 11, Harvard Apparatus; South Natick, MA). The syringe was coupled to the reservoir (Fig. 1). The injector was set to a constant speed, increasing the pressure in the syringe and thus in the reservoir. The resulting increase in flow was measured. The slope of the pressure ramp was 0.60 ± 0.06 cmH2O/s, allowing capacitance-free flow increase (12). Our setup did not allow us to reduce perfusion pressure to zero pressure, and therefore we had to extrapolate to Pint in most cases. The measured coronary pressure-flow relationships were fitted to a model described by Van Dijk et al. (22)
P<SUB><IT>x</IT></SUB><IT>=A×</IT>[1<IT>−</IT>exp(−F/F<SUB>0</SUB>)]<IT>+R×</IT>F<IT>+</IT>P<SUB>int</SUB> (1)
where Px is either Pinput or Pmv, F is total flow, and R, A, and F0 are parameters of the model: parameter A is the amplitude of the exponential function, R is the resistance in the linear part of the relation, and F0 is the curvature of the relation. With the use of this model, Pint can be determined in an objective way from the relation between F and Px (22). Pressure measurements using the servo-null technique were performed in microvessels of the papillary muscles. The measured local Pmv was plotted against total flow, resulting in a local pressure-flow relationship. The data were then fitted to Eq. 1.

Flow was expressed per gram of muscle weight. The muscle weight was calculated from the muscle dimensions and the density of cardiac tissue (1.06 g/cm3). It was assumed that local flow is a constant fraction of the total flow. From Eq. 1, it can be calculated that using a constant fraction of flow has no effect on the value of Pint and, therefore, total flow can be used to calculate Pint in the peripheral vasculature. This was also illustrated by Kanatsuka et al. (11), who reported the different flows at three levels of the vascular bed but still found the same Pint because they used aortic pressure in their relationships. The other values of Eq. 1 do not give meaningful information when total flow is used instead of local flow, and will therefore not be reported.

Statistics. All values are expressed as means ± SE. Comparisons between parameters from the total vasculature and from arterioles and venules were made with ANOVA, followed by Tukey's post hoc test for comparison between all groups. P values < 0.05 were considered significant.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Figure 2 shows a recording of a local pressure measurement (Pmv) in an arteriole with a diameter of 37 µm together with overall flow and Pinput as a function of time. Pinput was used to construct the pressure-flow relationship at the entrance, and Pmv was used to calculate the local pressure-flow relationships. Both entrance and local pressure-flow relationships in the same muscle are depicted in Fig. 3. These data were fitted to Eq. 1 (dotted line in Fig. 3). Figure 3 shows that the intercept pressure at the entrance (septal artery) of the muscle is ~20 cmH2O, whereas in the arteriole (37 µm) it is ~2 cmH2O. The average relative pressure (Pmv/Pinput) over the vasculature was calculated using Eq. 1 at a flow of 90 ml · min-1 · g-1. Pmv/Pinput was 0.61 ± 0.16 for the arterioles and 0.17 ± 0.03 for venules.


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  		Fig. 2.   Example of a recording from a microvascular pressure (Pmv) measurement. Pmv (top) was recorded in an artery with an inner diameter of 37 µm.



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  		Fig. 3.   Typical examples of pressure-flow relationships. The dotted line represents the result of a fit to Eq. 1. A: pressure-flow relationship in a perfused papillary muscle at the entrance. B: relationship between Pmv and total flow in the same muscle. Pmv was recorded in an artery with an inner diameter of 37 µm (see Fig. 2). Note that the fit to the model (Eq. 1) was performed on the inverse of these relationships.

Pmv was measured in vessels with a diameter ranging from 24 to 110 µm. The relationship between vessel diameter and Pint was tested with linear regression analysis. Because there was no significant relationship between those two parameters (P > 0.05) in arterioles and venules, respectively, we pooled the data for arterioles in one group and those for venules in another group.

The averages of the calculated Pint are given in Fig. 4. The intercept pressures of pressure-flow relationships at the entrance were significantly different from zero. The intercept in the septal artery (23.2 ± 4.4 cmH2O, n = 12) with a diameter ranging from 150 to 250 µm was significantly higher than that in arterioles ranging between 110 and 24 µm (1.7 ± 0.5 cmH2O, n = 6). The latter intercept pressure was also significantly different from zero. The intercept pressure (1.1 ± 1.1 cmH2O, n = 4) in venules with a diameter of 24-110 µm was not different from zero.


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  		Fig. 4.   Average data for the zero-flow pressure intercept (Pint) of the total (n = 12) and peripheral vasculature in perfused papillary muscles. Local measurements are divided into arterial (n = 6) and venous (n = 4) groups. **P < 0.01 vs. Pint at the entrance, as measured with an ANOVA with Tukey's post hoc test; dagger P < 0.05, significantly different from zero.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

We found that Pint is not the same throughout the vascular bed and is significantly lower in arterioles than in the septal artery. In venules, the intercept pressure was not different from zero. We could not show a relation between the vessel diameter (range 24-110 µm) and local intercept pressure. Thus two waterfalls appear to exist; the first vascular waterfall is located in arterioles larger than 110 µm, and the second is located in vessels smaller than ~25 µm.

Microvascular pressure. We were able to measure pressure at different sites in the vasculature of the rat right ventricular papillary muscle. The main advantage of using isolated perfused papillary muscle is that it does not depend on the perfusion for O2 supply (16). This means that perfusion pressure can be altered at will without affecting the oxygen supply. Our experiments were performed under maximal vasodilatation and in diastole. In crystalloid-perfused rat hearts at 100 mmHg (136 cmH2O), the flow is ~15 ml · min-1 · g-1 (16). In papillary muscle weighing ~1 mg, we found that the flow was 46.3 ± 8.0 ml · min-1 · g-1 (n = 12). This flow is probably too high because part of the septum is also perfused (16) but is not included in the weight. Therefore, it is difficult to make the distinction between muscle and septum.

Although significant heterogeneity of flow exists in the heart (3), it is unlikely that this is also true within the papillary muscle preparation. In this part of the heart, all muscle cells run in parallel with the capillaries. To determine an intercept in the smaller arterioles, total flow and local pressure were used. Therefore, we had to assume that local flow was a constant fraction of total flow. Even if heterogeneity exists in our preparation, it would not lead to different values for Pint as long as the fraction of total flow is constant. This is shown clearly in the dog subepicardium, where Kanatsuka et al. (11) measured red blood cell velocities at three levels of the vasculature and constructed pressure-flow curves with aortic pressure. The data of these authors show that the amount of flow (red blood cell velocity) does not affect the value of the pressure intercept when the same pressure is used in the pressure-flow relationships. This implies that the pressure-flow intercept we found is also independent of flow (see also METHODS). Although flow itself had no impact on the value found for Pint, we discarded all experiments with high flows (>90 ml · min-1 · g-1) because we suspected that in those preparations at least part of the flow was leaking through a cut side branch in the septum.

We evaluated if the pressure ramp was slow enough to exclude capacitative flow. Our change of pressure over time of ~0.6 cmH2O/s (0.04 mmHg/s) was considerably slower than what was shown to be necessary for a capacitance free relation by Aversano et al. (3 mmHg/s) (2). Thus we can assume that flow in our preparation was free of capacitance effects. This was confirmed by the fact that within a single experiment the same relationship was observed using both a pressure step and a ramp protocol (Fig. 5). We found the local pressure-flow relationships to be curved, whereas in dog hearts, Bellamy (4) found straight pressure-flow relationships. However, Aversano et al. (2) have shown that using an increasing pressure gives a more curved pressure-flow relation than using a decreasing pressure. Curved relationships in the arrested (diastolic) whole heart have been reported by several authors (1, 11, 13, 22). However, for the whole heart, other mechanisms may contribute to the curvature. A possible mechanism could be that decreased perfusion pressure causes a sequential "drop out" of perfusion of layers of the heart. This would lead to a decrease in the vascular volume perfused and increase the curvature of the pressure-flow relation, as was shown by Downey and Kirk (6). Another mechanism that may play a role is that a decrease of the intravascular pressure may result in decreased vessel diameter, and hence an increase of transmural pressure, thereby increasing the resistance leading to a curved pressure-flow relationship (18).


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  		Fig. 5.   Example of a local pressure-flow relationship within a single muscle. The relationship measured during a pressure ramp (closed circles) was not different from that with a stepwise increase in perfusion pressure (open circles).

Diastolic zero-flow pressure intercept. We evaluated the pressure-flow relationships at three levels in the vasculature of the papillary muscle at 80% Lmax. The results at the entrance are in agreement with our earlier data, where an overall diastolic Pint of 19.6 ± 6.6 cmH2O was found (10). In whole maximally dilated dog hearts, values of 12-15 mmHg (16-20 cmH2O) were reported (11, 13). Van Dijk et al. (22) showed a Pint of 20.4 ± 3.9 cmH2O in blood-perfused and 27.5 ± 5.6 cmH2O in Tyrode solution-perfused cat hearts. We found that Pint for arterioles between 24 and 110 µm was much smaller (~15 times) than in the septal artery. No correlation was found between Pint and diameter in the septal artery. Because the septal artery is 150 to 250 µm in diameter, this means that the large decrease in Pint is taking place in vessels between 150 and 110 µm, suggestive of a waterfall at this level.

We (10) found earlier that the intramyocardial pressure (IMP) in diastolic papillary muscle is ~1.8 ± 0.5 cmH2O (means ± SE). This is similar to the Pint we found in the arterioles. Measurements showed that in venules the Pint is not significantly different from zero. IMP have also been measured in whole heart preparations (8, 14). These data show that IMP in the ventricular wall is correlated with left ventricular pressure. This would suggest an IMP of zero in case of absence of ventricular pressure. Our results could be explained by formation of edema. However, a small IMP could be measured in the papillary muscle preparation without perfusion and apparent edema formation (9). In our experiments, care was taken to perfuse the preparation only in the case of a pressure measurement, thus minimizing edema formation.

To explain our results, we propose a model with two distinct waterfalls, somewhat in analogy to what Braakman et al. (5) suggested. The first waterfall has an intercept pressure of ~20 cmH2O and is located in arterioles between 110 and 150 µm in diameter. The second waterfall is located in vessels smaller than 24 µm, perhaps at the capillary level or at the postcapillary venules, and has a waterfall pressure of ~2 cmH2O equal to IMP (10). The first waterfall is probably caused by the mechanical properties of the arterioles larger than 110 µm (5). The second waterfall can be explained on the basis of IMP (10), although effects of surface tension cannot be ruled out (17).

There is evidence that IMP is closely related to ventricular pressure (8, 14). Extrapolation to zero left ventricular pressure gives a value of ~2 mmHg on the basis of the data of Heineman and Grayson (8). Our data and those of Heslinga et al. (10) suggest that, in our preparation without external (ventricular pressure), IMP is also slightly but significantly above zero. This might be due to the formation of edema. However, Heslinga et al. (9) have shown that even in unperfused papillary muscles (i.e., without edema), a significant IMP exists.

To find this second waterfall, closure of vessels is not necessary. This was shown by Sipkema and Westerhof (18), who used latex microtubes to study the effect of surrounding pressure on the pressure-flow relation of a small vessel. In this model, the external pressure is transmitted to the pressure inside the tube. At the distal end of the tube, both pressures will be equal due to the pressure drop over the tube. The collapsible end of the tube acts as a resistance to flow ("Starling resistor"). In this part of the tube, the transmural (internal - external) pressure is zero. The pressure in the horizontal part of the pressure-volume (pressure-diameter) relation, where large volume changes take place for small pressure changes, equals the value of the waterfall (Pint). This intercept is equal to the external (i.e., intramyocardial) pressure. Thus closure of vessels is not required to find a pressure intercept that is related to IMP.

Several authors (17, 21) have suggested that a venous waterfall exists in whole heart preparations. Recently, Aldea et al. (1) showed that changes in pressure in or around a diastolic heart increase Pint. This is accompanied by an increase in coronary venous pressure. These authors also found evidence for regional differences in Pint between the subendocardium and subepicardium. In our preparation, venous pressure is zero, but if venous pressure is high, it might overrule the second waterfall we observed.

In intact heart, it might well be that the ventricular pressure is the main determinant of the height of the second waterfall (8, 14). This could, in the heart, lead to regional differences in Pint, because it has been shown that there are regional differences in IMP values (15). This suggests that a second waterfall can exist, which is closely related to IMP. We therefore hypothesize that, during systole, the increase in IMP (10, 20) causes Pint in vessels smaller than 25 µm to increase, making the second waterfall pressure the dominating one.

In conclusion, we determined that Pint is ~15 times lower in arterioles with diameters smaller than 110 µm than in the feeding septal artery. Pint in arterioles between 24 and 110 µm is not size dependent, whereas in venules Pint is absent. We therefore propose a double waterfall model to explain the coronary Pint. One waterfall is located in arterioles larger than 110 µm and one waterfall is located between small arterioles and venules, possibly in the capillaries or postcapillary venules.


    ACKNOWLEDGEMENTS

This work was supported by The Netherlands Heart Foundation Grant 94-069 and by National Heart, Lung, and Blood Institute Grant HL-44399-01.


    FOOTNOTES

Address for reprint requests and other correspondence: J. P. Versluis, Laboratory for Physiology, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands (E-mail: versluis{at}physiol.med.vu.nl).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 5 December 2000; accepted in final form 5 July 2001.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1.   Aldea, GS, Mori H, Husseini WK, Austin RE, and Hoffman JI. Effects of increased pressure inside or outside ventricles on total and regional myocardial blood flow. Am J Physiol Heart Circ Physiol 279: H2927-H2938, 2000[Abstract/Free Full Text].

2.   Aversano, T, Klocke FJ, Mates RE, and Canty JM. Preload-induced alterations in capacitance-free diastolic pressure-flow relationship. Am J Physiol Heart Circ Physiol 246: H410-H417, 1984.

3.   Bassingthwaighte, JB, King RB, and Roger SA. Fractal nature of regional myocardial blood flow heterogeneity. Circ Res 65: 578-590, 1989[Abstract/Free Full Text].

4.   Bellamy, RF. Diastolic coronary artery pressure-flow relations in the dog. Circ Res 43: 92-101, 1978[Abstract/Free Full Text].

5.   Braakman, R, Sipkema P, and Westerhof N. Two zero-flow pressure intercepts exist in autoregulating isolated skeletal muscle. Am J Physiol Heart Circ Physiol 258: H1806-H1814, 1990[Abstract/Free Full Text].

6.   Downey, JM, and Kirk ES. Inhibition of coronary blood flow by a vascular waterfall mechanism. Circ Res 36: 753-760, 1975[Abstract/Free Full Text].

7.   Fox, JR, and Wiederhielm CA. Characteristics of the servo-controlled micropipet pressure system. Microvasc Res 5: 324-335, 1973[ISI][Medline].

8.   Heineman, FW, and Grayson J. Transmural distribution of intramyocardial pressure measured by micropipette technique. Am J Physiol Heart Circ Physiol 249: H1216-H1223, 1985[Abstract/Free Full Text].

9.   Heslinga, JW, Allaart CP, and Westerhof N. Intramyocardial pressure measurements in the isolated perfused papillary muscle of rat heart. Eur J Morphol 34: 55-62, 1996[ISI][Medline].

10.   Heslinga, JW, Allaart CP, Yin FCP, and Westerhof N. Effects of contraction, perfusion pressure, and length on intramyocardial pressure in rat papillary muscle. Am J Physiol Heart Circ Physiol 272: H2320-H2326, 1997[Abstract/Free Full Text].

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13.   Klocke, FJ, Weinstein IR, Klocke JF, Ellis AK, Kraus DR, Mates RE, Canty JM, Anbar RD, Romanowski RR, Wallmeyer KW, and Echt MP. Zero-flow pressures and pressure-flow relationships during single long diastoles in the canine coronary bed before and during maximum vasodilation. Limited influence of capacitive effects. J Clin Invest 68: 970-980, 1981.

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17.   Sherman, IA, Grayson J, and Bayliss CE. Critical closing and critical opening phenomena in the coronary vasculature of the dog. Am J Physiol Heart Circ Physiol 238: H533-H538, 1980.

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19.   Spaan, JAE Mechanical determinants of myocardial perfusion. Basic Res Cardiol 90: 89-102, 1995[ISI][Medline].

20.   Spaan, JAE, Breuls NP, and Laird JD. Diastolic-systolic coronary flow differences are caused by intramyocardial pump action in the anesthetized dog. Circ Res 49: 584-593, 1981[Free Full Text].

21.   Uhlig, PN, Baer RW, Vlahakes GJ, Hanley FL, Messina LM, and Hoffman JI. Arterial and venous coronary pressure-flow relations in anesthetized dogs. Evidence for a vascular waterfall in epicardial coronary veins. Circ Res 55: 238-248, 1984[Abstract/Free Full Text].

22.   Van Dijk, LC, Krams R, Sipkema P, and Westerhof N. Changes in coronary pressure-flow relation after transition from blood to Tyrode perfusion. Am J Physiol Heart Circ Physiol 255: H476-H482, 1988[Abstract/Free Full Text].

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Am J Physiol Heart Circ Physiol 281(5):H1913-H1918
0363-6135/01 $5.00 Copyright © 2001 the American Physiological Society


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