The leukopoietic cytokine granulocyte colony-stimulating factor increases blood flow to rat bone marrow.

The current knowledge concerning the blood supply to hematopoietic bone marrow during increased marrow metabolism is scanty. We have previously shown that an accelerated erythropoiesis in the awake rat is accompanied by a rapid increase in perfusion of the tibial marrow and its bony encasement. We have now measured blood flow to tibial marrow and bone in rats with stimulated granulopoiesis, caused by injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF). In awake, adult rats, blood flow was measured with the microsphere method before and at intervals during a 48-hour period after subcutaneous (s.c.) injection of rhG-CSF (10 micrograms/kg). Administration of rhG-CSF caused a marked leukocytosis, mostly due to an increase in blood granulocytes, amounting to 4 times the control value at 8 hours. Concomitantly, the perfusion of tibial marrow rose to about 200% of control by 8 hours before it declined toward baseline. Denervation of the marrow had no effect on this hyperemic response. The perfusion of tibial bone was apparently unaffected by rhG-CSF injection. We conclude that rhG-CSF injection increases blood flow to hematopoietic marrow, but not to bone. This may have important implications for marrow transplantation and drug therapy for patients with marrow failure.

Endogenous nitric oxide causes vasodilation in rat bone marrow, bone, and spleen during accelerated hematopoiesis.

There is a marked increase in blood flow to rat bone marrow during increased erythro- or granulopoiesis. Furthermore, stimulated erythropoiesis increases bone and splenic perfusion, whereas granulopoietic hyperactivity does not. The mechanism behind this hyperemia is unknown. Endogenous nitric oxide (NO) has been shown to be a potent vasodilator in many vascular beds, but its possible role in the regulation of bone marrow, bone, and spleen vascular resistance and perfusion has not been explored. With the radioactive microsphere method, we determined blood flow to bone marrow, bone, and spleen in awake rats. Eight rats were bled heavily (1.5% of body weight), eight others received 10 micrograms/kg recombinant human granulocyte colony-stimulating factor (rhG-CSF) subcutaneously, and eight other untreated rats served as controls. We used 300 micrograms/kg, intraaortal, of the potent NO synthase blocker N-monomethyl-L-arginine (L-NMMA) (Calbiochem, La Jolla, CA). The inhibition of NO formation was subsequently reversed with 1000 mg/kg intraaortal arginine. Marrow vascular resistance was reduced to approximately 30% of control baseline in the experimental rats 10 hours after hematopoietic stimulation with either bleeding or rhG-CSF. Concomitantly, marrow blood flow increased to about 260% of control baseline in the bled rats, while it almost tripled after rhG-CSF injection. Inhibition of NO formation increased marrow vascular resistance in all three groups. After L-NMMA treatment, marrow perfusion was reduced to about 50% of baseline in the bled and 75% in the rhG-CSF-treated rats, while perfusion in the controls remained apparently unaltered. These changes were completely reversed with arginine. The increases in vascular resistance after NO blockade could not be explained by a concomitant change in arterial blood pressure. L-NMMA increased the vascular resistance in the bone and spleen both in controls and in stimulated rats, but since arterial blood pressure rose proportionally, perfusion remained unchanged. We conclude that NO plays an important role in the regulation of both the normal bone marrow vascular tone and the vasodilation that occurs during accelerated hematopoiesis. NO apparently also regulates bone and splenic vascular tone, but less conspicuously than in the stimulated bone marrow.

Decreased blood flow to rat bone marrow, bone, spleen, and liver in acute leukemia.

An acute promyelocytic leukemia in the rat (BNML) has been used in model studies on pathogenesis and therapy of human acute myeloid leukemia. The blood supply to bone marrow during BNML development has hitherto not been examined, even though in general, blood flow to hematopoietic tissues might affect drug treatment and marrow transplantation regimes. We measured the perfusion of various organs during the course of the disease in untreated rats and in rats given one injection of cyclophosphamide treatment. Organ perfusion was measured with radioactive microspheres. Blood flow per gram tissue to the bone marrow, bone, spleen, and liver declined gradually during the leukemic progression, thus paralleling the growth of leukemic deposits. Cyclophosphamide treatment retarded, but did not reverse, the decreasing perfusion of these tissues.

Fluid Exchange in the isolated perfused lung.

The advantages of an isolated, perfused lung preparation in studies of transvascular fluid shifts are described. We find the permeability characteristics of the exchange vessels in the rabbit lung preparation to be similar to those obtained in lungs in situ. The filtration coefficient is similar during plasma and during Krebs-Ringer dextran T 70 perfusion. Therefore proteins in the perfusate do not modify the permeability of the exchange vessels in these lungs as had been reported for other vascular beds. Interstitial fluid pressure in both the alveolar walls and the alveolar corner regions increases with a rise in alveolar pressure. The result is a reduction in the fluid filtration rate under both zone-III and zone-I conditions. The resistance of the extravascular pathway and the fluid pressure in the periarterial/perivenous spaces both appear to be reduced when lung volume is increased by a reduction in pleural pressure. The net effect of positive airway pressure on the transvascular fluid exchange will depend on the relative contribution of the alveolar pressure effects and the lung volume effects. Fluid reabsorption can be observed to occur in the isolated, perfused rabbit lung. This reabsorption does not take place at the level of the loose perivascular tissue spaces since the interstitial fluid pressure at these sites is much lower than the microvascular pressure. We suggest that fluid reabsorption takes place at the thick part of the air-blood barrier, which, most likely, has a higher fluid pressure.

Micropuncture pressure in small arteries or veins of perfused rabbit lungs.

Until now, direct micropuncture measurements of vascular pressure in lung have been limited to small vessels less than 100 microns on the pleural surface. On the other hand, direct pressure measurements using small catheters (less than 1-mm OD) in pulmonary vessels have been limited to those greater than 1.2 mm. We measured pressure in intermediate-sized microvessels (300-700 microns) using the micropuncture method in isolated perfused rabbit lungs. These microvessels are located 2 or 3 mm beneath the pleura. We exposed them by microsurgery and punctured the relatively thick-walled vessels with specially configured micropipettes. We exposed one pulmonary microvessel in each rabbit lung by microsurgery on the left middle lobe. In 15 rabbit lungs we measured pressure in a total of six small arteries (275- to 470-microns diam) and nine small veins (300- to 700-microns diam) under high zone 3 conditions, near the zone 2/3 boundary. We found approximately 35% of the total pulmonary vascular pressure drop in arteries greater than 275-microns diam and 7% in veins greater than 300-microns diam. In veins greater than 500-microns diam, there was no measurable pressure drop. After the measurements, we froze the lung and confirmed that there was no detectable interstitial or alveolar edema in the cross sections of the punctured site. Our data are compatible with those of other investigators who have used isolated perfused rabbit lungs under similar experimental conditions.

Lung microvascular pressure profile measured by micropuncture in anesthetized dogs.

We have micropunctured the lung in the open thorax of 17 anesthetized dogs to measure microvascular pressure. After intravenous pentobarbital sodium (25 mg/kg), we exposed the left lung through a wide left thoracotomy, which required rib excision. Through a double-lumen endotracheal tube, we ventilated the right lung to maintain normal blood gases and pH while we held the left lung motionless at an inflation pressure of 5 cmH2O. To reduce motion on the surface of the left lower lobe, we resected the left upper lobe, placed a Plexiglas baffle between the lobe and the heart, and held the lobe surface in a suction ring. In accordance with procedures we have previously described, we micropunctured subpleural vessels to measure microvascular pressure. At base line when alveolar pressure exceeded left atrial pressure (zone 2 conditions), 21, 38, and 41% of the total pressure drop occurred, respectively, in the arterial, microvascular, and venous segments. When we raised left atrial pressure above alveolar pressure (zone 3 conditions), the corresponding pressure drops were 30, 55, and 20% of total. The blood flow in the superficial layer of the lung averaged 15% less than the flow in the deeper layers as measured by distribution of 99mTc-albumin macroaggregates. We conclude that the intact and the isolated lung preparations in dog exhibit similar distributions of subpleural microvascular pressure.

No gravity-independent gradient of blood flow distribution in dog lung.

The existence of a major gravity-independent gradient of blood flow in lungs has recently been described based on single photon emission computed tomography after intravenous injection of radioactively labeled macroaggregates. We wanted to test this hypothesis of a major gravity-independent gradient in lung blood flow in experiments with direct measurement of macroaggregate distribution in the dog lung. In six anesthetized (4 prone spontaneously breathing, 2 mechanically ventilated) dogs we injected 111In-labeled albumin macroaggregates intravenously. We killed the dogs, removed, inflated, and froze the lower lobes. We sliced the lobes 1 cm thick and made gamma camera images of the slices. We then cut three or four slices in each lobe into two or three concentric layers and measured the radioactivity per gram of tissue in a well-type gamma counter. In three of the dogs we also labeled the red cells (99mTc) so that blood volume in each sample could be determined. The gamma camera images were acquired on a 64 X 64 matrix with 4 X 4 mm pixels. On the numeric printouts from the individual slices we made two or three concentric layers and calculated activity per pixel in each layer. Neither by the well counting nor by the pixel analysis of the gamma scans did we detect any gravity-independent distribution of blood flow. With the well counting the distribution was the same whether macroaggregate activity was expressed per gram of tissue or per gram of blood-free tissue. We conclude that by direct measurements no major gravity-independent gradient of pulmonary blood flow can be detected in dog lungs.

Effect of catheter size on pressures recorded in small pulmonary veins in dog lung.

Controversy continues about the contribution of the veins to pulmonary vascular resistance. From data obtained in studies using intravascular catheters, it appears that a major fraction (up to 44%) of the total pulmonary vascular pressure drop resides in larger (greater than 1.0 mm diam) veins, whereas micropuncture data and various models give much less pressure drop. Theoretically, artifactual pressure drops can be obtained if an intravascular catheter partly obstructs the vessel. We made measurements of pressure in the same lung vein with two different-sized catheters (1.2 and 0.6 mm OD, respectively). In paired experiments the larger catheter always measured a higher pressure than the smaller one, except close to the large lobar vein outlet. In some of the experiments we measured the diameter of the vessel containing the indwelling catheter by freezing the lung and then serial-sectioned the frozen lung. From these data we could infer that the range of vein diameter in the which the smaller catheter measured a lower pressure was 1.5-4 mm. We conclude that the larger catheter overestimated the pressure because of greater obstruction. The pressures obtained with the smaller catheter suggest that little (less than 10%) of the total pulmonary vascular resistance resides in veins larger than approximately 1 mm diam under zone 3 baseline conditions.

Influence of centrifugal sinus nerve activity on carotid body catecholamines: microphotometric analysis of formaldehyde-induced fluorescence.

The effects of centrifugal activity in the carotid sinus nerve (CSN) on the intensity of formaldehyde-induced fluorescence of carotid body were examined in cat. Measurements of intensity were obtained from 21 to 56 sections of each carotid body with a microscope photometer attached to a fluorescence microscope. Comparisons were made between the two carotid bodies removed from each cat. In one series of experiments, one carotid body (CSN intact) served as control, while the experimental carotid body was on the side on which centrifugal activity was increased by electrical stimulation of the peripheral end of the cut CSN. In a second series, centrifugal CSN activity was increased by hypoxemia; one CSN was transected (control) and the other was left intact (experimental). In untreated cats, fluorescence intensity was significantly higher on the side with increased centrifugal CSN activity. In cats treated with either MK486, which inhibits conversion of L-DOPA to dopamine, or reserpine, increased centrifugal CSN activity caused a significant decrease in intensity of type I cells. These findings indicate that centrifugal discharges regulate, in part, the synthesis and release of catecholamines by type I cells of the carotid body.

Improved haemodynamics with increased compression-decompression rates during ACD-CPR in pigs.

The haemodynamic effects of variations in the compression-decompression frequency, 60, 90 and 120 min(-1) during ACD-CPR, were tested in a randomized cross-over design during ventricular fibrillation (VF) in 12 anaesthetized pigs (17-22 kg) using an automatic hydraulic chest compression-decompression device. There were significant increases with increasing frequency for mean (+/- S.D.) carotid blood flow (17 +/- 5, 25 +/- 9 and 36 +/- 12 ml min(-1), transit time flow probe), cerebral blood flow (17 +/- 7, 30 +/- 17 and 40 +/- 13 ml min(-1) 100 g(-1), radionuclide microspheres) and mean aortic pressure (34 +/- 8, 37 +/- 10 and 43 +/- 7 mmHg), respectively. Myocardial blood flow (radionuclide microspheres) and diastolic coronary perfusion pressure, CPP, increased significantly from 60 to 90 min(-1) with no further significant increase to 120 min(-1) (28 +/- 13, 46 +/- 23 and 49 +/- 19 ml min(-1) 100 g(-1) and 25 +/- 8, 31 +/- 11 and 32 +/- 9 mmHg, respectively). Renal and hepatic blood flow also increased with increasing rate. No significant differences in the expired CO2 levels were observed. In conclusion increasing the compression-decompression frequency from 60 to 90 and 120 min(-1) improved the haemodynamics during ACD-CPR in a pig model with VF.

Effect of different compression--decompression cycles on haemodynamics during ACD-CPR in pigs.

The haemodynamic effects of variations in the relative duration of the compression and active decompression (4 cm/2 cm) during active compression-decompression cardiopulmonary resuscitation (ACD-CPR), 30/70, 50/50 and 70/30, were tested in a randomized cross-over design during ventricular fibrillation in seven anaesthetized pigs (17-23 kg) using an automatic hydraulic chest compression-decompression device. Duty cycles of 50/50 and 70/30 gave significantly higher values than 30/70 for mean carotid blood flow (32 and 36 vs. 21 ml min-1, transit time flow probe, cerebral blood flow (30 and 34 vs. 19, radionuclide microspheres), mean aortic pressure (35 and 41 vs. 29 mmHg) and mean right atrial pressure (24 and 33 vs. 16 mmHg). A higher mean aortic, mean right atrial and mean left ventricular pressure for 70/30 were the only significant differences between 50/50 and 70/30. There were no differences in myocardial blood flow (radionuclide microspheres) or coronary perfusion pressure (CPP, aortic-right atrial pressure) between the three different duty cycles. CPP was positive in both the early and late compression period and during the whole decompression period. The expired CO2 was significantly higher with 70/30 than 30/70 during the compression phase of ACD-CPR. Beyond that no significant differences in the expired CO2 levels were observed. In conclusion a reduction of the compression period to 30% during ACD-CPR reduced the cerebral circulation, the mean aortic and right atrial pressures with no effect on the myocardial blood flow of varying the compression-decompression cycle.

Effects of various degrees of compression and active decompression on haemodynamics, end-tidal CO2, and ventilation during cardiopulmonary resuscitation of pigs.

UNLABELLED: The effects of various degrees of compression and active decompression during cardiopulmonary resuscitation were tested in a randomized cross-over-design during ventricular fibrillation in eight pigs using an automatic hydraulic chest compression device. Compared with 4/0 (compression/decompression in cm), mean carotid arterial blood flow rose by 60% with 5/0, by 90% with 4/2 and 4/3, and 105% with 5/2. Two cm active decompression increased mean brain and myocardial blood flow by 53% and 37%, respectively, as compared with 4/0. Increasing standard compression from 4 to 5 cm caused no further increase in brain or heart tissue blood flow whether or not combined with active decompression. Tissue blood flow remained unchanged or decreased when active decompression (4/3) caused that 50% of the pigs were lifted from the table due to the force required. Myocardial blood flow was reduced with 5/0 vs. 4/0 despite no reduction in end decompression coronary perfusion pressure ((aortic-right atrial pressure) (CPP), (7 +/- 8 mmHg with 4/0, 14 +/- 11 mmHg with 5/0)(NS)). End decompression CPP increased by 186% with 4/2 vs. 4/0, by 200% with 4/3, and by 300% with 5/2. Endo-tracheal partial pressure of CO2 was significantly increased during the compression phase of active decompression CPR compared with standard CPR. Active decompression CPR generated an significantly increased ventilation compared with standard CPR. CONCLUSION: Carotid and tissue blood flow, ventilation, and CPP increase with 2 cm of active decompression. An attempt to further increase the level of active decompression or increasing the compression depth from 4 to 5 cm did not improve organ blood flow.

Regional heterogeneity of myocardial blood flow within the rabbit left ventricle during haemorrhagic hypotension.

Several studies have reported an extensive regional heterogeneity in myocardial blood flow. The reported coefficients of variation for regional myocardial perfusion range from about 0.2 to 0.4 in normotensive animals. The spatial distribution of myocardial perfusion during haemorrhagic hypotension seems not to have been assessed. The goal of the present study was to determine the regional heterogeneity in myocardial blood flow within the rabbit left ventricle during normal conditions and after haemorrhagic hypotension. Radioactive microspheres were infused into the left ventricle in barbiturate anaesthetized rabbits over either 30 or 120 sec. The haemorrhagic hypotension was induced by bleeding, so that mean arterial blood pressure was reduced to about 50% of control. The left ventricles were divided into samples of about 0.025 g each. Regional heterogeneity in the blood flow was expressed as the coefficient of variation corrected for the Poisson distribution of microspheres (CVc). The CVc was 0.37 +/- 0.09 (mean +/- SD) during control and 0.41 +/- 0.11 after bleeding, the CVc obtained after bleeding being somewhat higher than during control (P < 0.05). We obtained a high correlation coefficient (tau about 0.68) between regional perfusion values at control and after bleeding which indicates a stable perfusion pattern within the myocardium. We conclude that the regional distribution of coronary blood flow within the left ventricle is markedly heterogenous during control condition and that this pattern is not changed during haemorrhagic hypotension.

Protein concentration in lymph.

A brief review is given on the problem of protein concentration in lymph versus protein concentration in interstitial fluid. The possibility of a concentrating ability of the lymphatics is discussed in the light of recent investigations. It is concluded that the final answer to the problem is not known, but that substantial evidence indicate that the protein concentration in lymph and in the interstitial fluid from which the lymph originate is similar.

On the existence of stretchable pores in the exchange vessels of the isolated rabbit lung preparation.

In the present work our aim has been to seek evidence for or against the existence of stretchable pores in the exchange vessels of the lungs. In isolated rabbit lungs ventilated by positive pressure and perfused with homologous blood we performed repeated tests with fluid filtration from the exchange vessels. In these tests the outflow pressure was elevated to specific values for periods of 6 min. The rate of weight gain of the preparation during the last 2 min of each test period was taken as the rate of fluid filtration from the exchange vessels. We found a linear relationship between rate of filtration and outflow pressure in the range from 5 to 20 mm Hg. This indicates that the hydraulic conductivity of the exchange vessels did not change with outflow pressure and thus that no pore stretching occurred within this pressure range. An abrupt increase in filtration rate took place when the outflow pressure was set at 25 or 30 mm Hg. The hydraulic conductivity of the exchange vessels was therefore probably increased at these high pressures. Since in 3 lungs this increase in filtration rate was fully reversible we suggest that a stretching of pores in the exchange vessels of the lungs contributed to the increase in hydraulic conductivity. This stretching of pores occurred only when vascular pressures were at or above the upper level of the physiological pressure range for the lungs.

Low concentrations of inhaled nitric oxide do not improve oxygenation in patients with very severe chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway narrowing that is most frequently inhomogeneously distributed. Ventilation/perfusion (V/Q) mismatch may explain much of the hypoxemia in patients with advanced disease. A potential treatment strategy would be to redistribute blood flow to well-ventilated lung regions in order to decrease V/Q mismatch. It has been suggested that inhaled nitric oxide (iNO) in physiologic concentrations ( approximately 100 p.p.b.) could act as a local vasodilating agent in well-ventilated lung regions. To test this, we included 10 volunteer patients with very severe COPD in this study. METHODS: NO was mixed with O(2) and N(2) and administered through a face mask. The partial pressure of inspired oxygen (P(i)o(2)) did not change by more than +/- 0.5 kPa from the room air value. NO was given in 15-min periods at concentrations of approximately 0, approximately 40, approximately 400, approximately 4000 and approximately 40,000 p.p.b. (random order). During each NO exposure, arterial blood gases, methemoglobin and systemic blood pressure were measured every fifth minute. RESULTS: None of the patients reported subjective effects of the different gas mixtures. The partial pressure of oxygen in arterial blood (P(a)o(2)) did not change by more than +/- 1.2 kPa from the baseline value, and there was no correlation between the change in P(a)o(2) and iNO concentration. No significant changes were found in blood pressure or methemoglobin during iNO. CONCLUSION: No significant effect of iNO at concentrations up to 40,000 p.p.b. in inspired gas was found on arterial blood gases. This indicates that neither low nor high concentrations of iNO improve oxygenation in patients with very severe COPD.

Pulmonary O2 transfer during pulsatile and non-pulsatile perfusion.

The importance of the perfusion pattern for the oxygen transfer has been examined in isolated rabbit lungs perfused with plasma at constant volume inflow. The lungs were ventilated with constant tidal volume and constant end-expiratory pressure. Following a standardized rise in FIO2 the rate of rise in pulmonary venous PO2 (delta PO2/delta t) was measured during alternately pulsatile and non-pulsatile perfusion in normal lungs and in lungs made edematous by elevation of left atrial pressure. In normal lungs there was no difference in delta PO2/delta t when the two modes of perfusion were compared. In edematous lungs delta PO/delta t was statistically higher during pulsatile perfusion, indicating a beneficial effect of flow- and pressure pulsations, e.g. a better distribution of V/Q ratios throughout the lungs. In a separate series of expts. the advancement of a high O2 front through the airways was measured, and the two perfusion patterns compared. Since no difference was found, we suggest that the phenomenon of "cardiogenic gas mixing" in the airways in vivo is a result of a direct action of the heart on the lungs rather than arterial pulsations.

Determinants of transvascular fluid shifts in zone I lungs.

We studied the fluid shifts in isolated, plasma-perfused rabbit lungs kept completely within zone I. The rate of fluid filtration or reabsorption was determined gravimetrically. A rise in alveolar pressure at constant pleural and vascular pressures reduced th rate of filtration or increased the rate of reabsorption in seven of eight lungs. In seven of seven lungs a reduction in pleural pressure at constant alveolar and vascular pressures increased the rate of filtration or decreased the rate of reabsorption. Thus, a given rise in lung volume had opposite effects depending on whether this rise was caused by an increased alveolar or reduced pleural pressure. Therefore, the exchange vessels studied cannot be true extra-alveolar vessels, which always expand (reflecting a rise in transmural pressure) with a rise in lung volume. When alveolar and pleural pressures were equally increased at constant vascular pressure, the rate of filtration was reduced in four of four lungs. The results can be explained through the existence of exchange vessels situated neither in the alveolar septae proper nor among the true extra-alveolar vessels. The vessels in the alveolar junctions are the most likely candidates.

The importance of flow pulsatility for the rate of transvascular fluid filtration in lungs.

1. The rate of transvascular fluid filtration has been studied with a gravimetric technique in isolated perfused rabbit lungs during periods of elevated left atrial pressure (PLA). 2. Fluid filtration was expressed as the filtration coefficient, Kf (g/min x 100 g bloodless lung x mmHg PLA) and determined during alternately pulsatile and non-pulsatile perfusion in six zone III and three zone II/I lung preparations. Perfusion pattern was changed without interruption of flow. Mean in- and outflow pressures were kept constant. 3. In all the lungs it was found that Kf was higher during pulsatile than during non-pulsatile flow (P less than 0.01). Mean Kf (+/- S.E. of mean) for the zone III preparations was 0.42 (+/- 0.089) and 0.27 (+/- 0.057) for pulsatile and non-pulsatile perfusion, respectively. The corresponding figures for the zone II/I preparations were 0.11 (+/- 0.035) and 0.04 (+/- 0.030). 4. We suggest that the difference is due to a larger filtration area and/or a higher mean microvascular hydrostatic pressure during pulsatile than during non-pulsatile flow and not to a rise in hydraulic conductivity due to pressure pulsations ('stretched pores'). 5. When the water-exchange function of the lung is considered, flow pattern should be taken into account as an entity in its own right in addition to the steady state or the mean component of blood flow.

Fractals describe blood flow heterogeneity within skeletal muscle and within myocardium.

A marked perfusion heterogeneity exists within single skeletal muscles and within the left ventricular (LV) myocardium. The relative dispersion (RD) of blood flows to regions < 1 g amounts to approximately 0.35 in both organs in rabbits. RD is changed with refinement of spatial resolution because the observed variance in regional flows increases. It has been shown with fractal analyses that the fractal dimension (D) can describe the relationship between the measured RD and size of the region studied within both the myocardium and the lung. A similar study has not been done with skeletal muscle. Barbital-anesthetized rabbits, cats, and sheep were used. Regional blood flow distribution was assessed with the microsphere method. Microsphere deposition in organ regions was determined after successive regrouping of either the LV or one skeletal muscle into various sized regions. We found that the perfusion patterns could be described with fractals for both organs, with the corresponding D values of 1.22-1.37 for the myocardium and 1.30-1.46 for muscle. It appears that fractals also yield a good description of blood flow distribution within skeletal muscle. In rabbits, D for myocardium was strongly correlated to the D for muscle (correlation coefficient = 0.98). This surprising finding of the strong correlation in D sampled from two organs originating from the same rabbit has hitherto not been reported.