Bone Marrow Pressure in Leukemic and Non-Leukemic Patients

Abstract

It has been a frequent observation that many patients with leukemia and multiple myeloma bleed freely through the marrow needle at the time of bone marrow aspiration although hemorrhagic tendencies may not be present clinically. In addition , throbbing bone pain and bone tenderness are not infrequently observed in these patients (1). Such clinical observations suggest that some degree of pressure elevation may be present in the marrow cavity in these diseases. It was believed of interest to determine the pressure relationships within the human marrow cavity under a variety of physiologic stimuli. MATERIALS AND METHODS The marrow pressures of 14 patients with neoplastic diseases having essentially normal marrows, as determined by microscopic examination, and of 10 patients with leukemia and one patient with multiple myeloma were determined by means of recording strain gauges attached to clinical bone marrow needles. The patients were studied under resting but not basal conditions, without previous sedation. The pressure in both the sternal and iliac crest marrows was measured in most patients, either simultaneously or serially. The sternal site was at the level of the second interspace, and the iliac crest at a site two centimeters posterior to the anterior superior iliac spine. The usual precautions of sterility and local procaine anesthesia of skin and periosteum were employed. A bonded SR4 wire resistance strain gauge and recording apparatus developed for clinical pressure measurements by Bierman and Jenkins (2) were employed for pressure determinations. The gauge was connected directly to the bone marrow needle after the needle and gauge chamber had been filled with heparin-saline solution. The saline within the manometer was equalized with the ambient pressure, after which the chamber was sealed. The output of the strain gauge was connected to a strain indicator and photographically recorded with a multiple channel recording oscilloscope. The Turkel-Bethell bone marrow needle employed in these studies had a 14-gauge bore and was equipped with a trephine stylette which made it useful for removing bony spicules which frequently entered the needle during its implantation. After implantation, the needle was filled with heparin-saline solution, care being exercised to exclude air bubbles. It was found necessary to premedicate the patients with 50 to 100 mg. of heparin intravenously shortly before the studies to prevent clotting within the needle in the marrow. Smaller amounts of heparin were used in patients with leukemia, or completely omitted where manifest bleeding tendencies existed. A modified strain gauge strapped over the lower chest cage was utilized as a pneumotachometer, and a single lead EKG tracing was made in each patient for pulse de-terminations. The marow pressure, respiratory rate and amplitude, and EKG record were simultaneously recorded photographically. The marrow pressures were studied with the patients at rest in supine position, during exaggerated respiration, coughing, Valsalva and Mueller...

BONE MARROW BLOOD VOLUME AND TOTAL RED CELL MASS OF THE GUINEA‐PIG AS DETERMINED BY 59Fe‐ERYTHROCYTE DILUTION AND LIQUID NITROGEN FREEZING

“…There is considerable evidence indicating that the marrow arteriolar tone is under nervous control [Drinker and Drinker, 1916;Petrakis, 1954;Stein et al, 1958;Herzig and Root, 1959;Brown-Grant and Cumming, 1962] but the general patterns of marrow vascular response are not clear. In the 'high activity' marrow following haemorrhage the marrow sinusoids become considerably dilated [Branemark, 1959] and the intramyeloid pressure has been reported to fall [Herzig and Root, 1959].…”

“…In the 'high activity' marrow following haemorrhage the marrow sinusoids become considerably dilated [Branemark, 1959] and the intramyeloid pressure has been reported to fall [Herzig and Root, 1959]. In human leuksemia marrows both the intramyeloid pressure and the blood flow rate may be increased [Petrakis et al, 1953;Petrakis, 1954]. In hypoxia the marrow blood flow has been reported to increase [Cumming, 1962] but the intramyeloid pressure falls [Kalser et al, 1951].…”

“…At 3 hr. after the injection of labelled erythrocytes there was evidence of a selective pooling in the spleen and bone marrow of recipient animals.The whole body blood volume was calculated to be 5-91 ml./100 g. body weight and the ratio of body haematocrit to cardiac haematocrit was 0846.A comparison of the numbers of circulating erythrocytes in marrow (isotope dilution technique) with total erythrocyte numbers determined in suspensions of disrupted marrow was in accord with the view that the non-nucleated, non-reticulated marrow erythrocytes are intravascular.RECENT observations of the detailed structure of the bone marrow vascular bed [Zamboni and Pease, 1961;Pease and Zamboni, 1962] have been supplemented by a number of functional studies, including direct visualization by vital microscopy [Kinosita et al, 1956; Brainemark, 1959] and relative measurements of marrow blood flow [Petrakis et at., 1953;Laing and Ferguson, 1959;Cumming, 1962;Brown-Grant and Cumming, 1962] and intramyeloid pressure [Kalsar et al, 1951;Petrakis, 1954;Stein et al, 1958;Herzig and Root, 1959]. These studies have shown the marrow vascular bed to be a highly labile system [Branemark, 1959;Zamboni and Pease, 1961] which not only responds to local and general pressor and depressor stimuli [Petrakis, 1954;Stein et al, 1958;Herzig and Root, 1959;Cumming, 1962] but also shows changes in blood flow or mean intramyeloid pressure * These studies were supported in part by U.S.…”

“…These studies have shown the marrow vascular bed to be a highly labile system [Branemark, 1959;Zamboni and Pease, 1961] which not only responds to local and general pressor and depressor stimuli [Petrakis, 1954;Stein et al, 1958;Herzig and Root, 1959; Cumming, 1962] but also shows changes in blood flow or mean intramyeloid pressure in conditions of altered marrow function, e.g. hypoxia [Kalser et al, 1951;Cumming, 1962], leukeemias [Petrakis et al, 1953; Petrakis, 1954] and following haemorrhage [Branemark, 1959; Herzig and Root, 1959]. Perfusion experiments have shown the rate of leucocyte release from the marrow to be partially related to the flow rate .…”

Increased pressure alters plasma membrane dynamics and renders acute myeloid leukemia cells resistant to daunorubicin

“…A pressure of 310 mmHg above atm corresponds to less than 0.5% of the maximum pressure acting on the head of the femur of an upright 160 lb person, and therefore, would be physiologically relevant as erosion of the trabeculae from leukemic infiltration increases sensitivity to external forces. 1,2 We found that the growth and viability of these cell lines did not change at high pressure ( Figure 1A). Next, we explored the impact of increased pressure on the sensitivity of these cells to three anthracyclines used in the treatment of AML: daunorubicin, idarubicin, and mitoxantrone.…”