Regulation of extracellular volumes and interstitial pressure within the rat bone marrow
Research field:Cardiovascular physiology
Authors:Iversen PO, Heyeraas KJ, Berggren E, Nicolaysen G
Address of presenting
author:		Institute for Nutrition Research, University of Oslo, PO Box 1046, 0316 Oslo, Norway
E-mail:poiversen@hotmail.com
Phone:47 22 85 13 91
Fax:47 22 85 13 98
Text of abstract Introduction
Treatment of patients with bone marrow failure may include administration of various haematopoietic growth factors. A common side effect is pain at the site of haematopoietic activity e.g. in the rib cage or the long bones (Gudi et al. 1995). Possibly may the enhanced haematopoietic activity within the marrow lead to increased vascular distension and also to increased transport of fluid from the vascular compartment into the interstitial space. In the apparently low compliant bone marrow even a small increase in extracellular fluid volume, due to increased blood volume or increased capillary filtration, may raise intramedullary interstitial fluid pressure and thus cause pain. The marrow is richly innervated (DePace & Webber 1975), and enhanced metabolism within the haematopoietic bone marrow caused by exogeneous cytokines increases blood flow to the rat bone marrow (Iversen, 1992). We now wanted to examine vascular volume and interstitial fluid volume and -pressure within the bone marrow.

Methods
Measurements were conducted in barbiturate anaesthetized Wistar rats. To determine intravascular volume (IVV) we used radiolabelled tracers (microspheres and low density lipoprotein particles) and Fe-tagged erythrocytes. For interstitial fluid volume (IFV) measurements we applied ethylene-diamine-tetraacetate. Interstitial fluid pressure (IFP) in the tibial marrow was recorded with micropipettes connected to a servocontrolled counter-pressure pump system (Wiederhielm et al. 1964).

Results
Both the microspheres and the lipoprotein particles yielded estimates of IVV of about 1 ml 100 g-1 tissue. IFV at baseline was about 6 ml 100 g-1 tissue. Following a brief reactive hyperaemia induced by clamping a femoral artery, IVV increased to about 2.5 ml 100 g-1 tissue. Simultaneously IFV decreased with about 1.5 ml 100 g-1 tissue indicating that total extracellular volume within the bone marrow did not change appreciably. Baseline bone marrow IFP was 9.7 mmHg. A brief reactive hyperaemia led to a transient 2.5-fold increase in IFP, while hypovolaemic hypotension induced by a marked blood loss reduced the IFP to about 50% of control measurements.

Conclusions
Our data suggest that extracellular volumes and interstitial fluid pressure within the bone marrow of intact rats can be measured with tracer methods and the micropuncture technique. The baseline values and the responses of IVV, IFV and IFP during changes in blood flow to the bone marrow are compatible with those for a low-compliant tissue. The increase in IFP measured after vasodilation might possibly explain the pain observed in patients after treatment with various haematopoietic growth factors.

References
DePace, D. M. & Webber, R. H. 1975. Acta Anat 93, 1-18
Gudi, R., Krishnamurthy, M. & Pachter, B. R. 1995. Ann Int Med 123, 236-237
Iversen, P. O. 1997. Acta Physiol Scand 159, 269-276
Wiederhielm, C. A., Woodbury, J. W., Kirk, S. & Rushmer, R. F. 1964. Am J Physiol 207, 173-176

Keywords:haematopoiesis, interstitium, pressure, vasodilation, volume

Created 2000-04-27