CARDIOVASCULAR LABORATORY

(ARTERIAL PHYSIOLOGY)

Barry S. Gow

This laboratory studies the physiology of arteries and vascular cells. The major focus at present is on vascular hyperplasia, particularly the role of haemodynamic factors such as shear stress and cyclic stretching of arterial cells.

RESEARCH in 1993

Role of endothelium in post-stenotic dilatation

Experiments done in 1992 in which the endothelium was removed from the thoracic aorta of rabbits did not answer unequivocally the question of whether endothelium was essential for the poststenotic dilatation (PSD) to occur. While the aorta could be successfully denuded with the aid of a specially designed instrument, the intercostal ostia could not be, and regeneration of the aortic endothelium occurred, spreading from the borders of the ostia. To avoid this problem preliminary experiments were done on the carotid artery, placing a stenosis ring around the vessel after removal of the endothelium. Unfortunately, in all cases the vessel subsequently thrombosed, and the project was therefore suspended temporarily.

Development of dynamic cell culture module

It was decided to direct the entire research effort into the Co-operative Research Centre (CRC)-funded project on vascular hyperplasia. A flow module was designed previously by the Laboratory to permit cultured endothelial and smooth muscle cells to be subjected to cyclic shear stress and to cyclic tensile stretch, thus mimicking the haemodynamic conditions under which such cells normally function. The module has undergone considerable modification since its initial design, but continues to use a flow channel of rectangular cross section, the floor of which is an elastomeric sheet capable of being cyclically stretched by a stepper motor. It has its own water jacket allowing it to be placed on a microscope stage where cellular growth can be monitored.

Calibration of flow channel: Since shear stress depends on velocity profile it was essential that the flow conditions of the dynamic cell culture module (DCCM) be accurately determined. Preliminary measurements using a laser-doppler anemometer in collaboration with D. Hadzismajlovic and C.D. Bertram from the Univ. of N.S.W. established laminar flow conditions within the channel under steady flow. A special version of the DCCM required construction for such tests due to the necessity of providing a laser light path through the side of the channel.

Flow delivery System: The prototype flow delivery system consisted of a peristaltic pump, a 0.2 µm filter, an arterial windkessel, the DCCM, a 'venous' collecting reservoir and appropriate series resistances to maintain physiological pressures within the module. Pressures and flow could be monitored continuously in this apparatus.

RESEARCH PLANNED for 1994

Endothelium

It is intended to refine the DCCM such that the membrane within it can be cyclically stretched. Further tests using the module specially developed to allow use of the laser doppler anemometer will be carried out to establish the velocity profiles for oscillatory flow. Once these tests have been completed and the flow rig completely evaluated, the apparatus will be sterilized and used to culture endothelial cells, first under static conditions and then using oscillatory flow. Rates of growth, altered morphology and degree of adherence to the elastomer will be measured. Measurement of rates of prostacyclin production are also planned.

Vascular smooth muscle cells

The effect of cyclic stretch on smooth muscle cell function will to begin with be determined independently of the effects of flow, by first developing a special culture chamber in which a strip of elastomer seeded with muscle cells can be stretched. Effects of stretch on modulation of cell phenotype will be observed. Subsequently, the effects of flow will be observed, as well as effects of flow and stretch.

PERSONNEL in 1993 and 1994

Dr Barry S. Gow		Associate Professor (in-charge) 	University      1973-
Carolyn Murtagh		Research Assistant, 3/5			CRC		Sep 1993-
Rodney James		BMedSc(Hons) 		       				1994
Steven Koh		BSc(Med)(Hons) 		       				1994
COLLABORATIONS

Pulse wave attenuation in arteries: Dr C. Bertram, Centre for Biomedical Engineering, Univ. of N.S.W. (1989-present)

Influence of haemodynamic factors vascular hyperplasia: Prof. K. Schindhelm, Centre for Biomedical Engineering, Univ. of N.S.W. (co-leader, with Dr Gow, of Project 1.3 Cooperative Research Centre on Cardiac Technology; also includes, Royal North Shore Hospital, Univ. of Technology, Sydney, and C.S.I.R.O. Division of Biomolecular Engineering) (1991-present).

FACILITIES

The Laboratory is located in rooms 265-267 of the Anderson Stuart Building. Dr Gow's office is room 268. The lab has a surgical operating and experimental facility for large animals. It contains an X-ray image intensifier, cardiac and arterial catheterization equipment, apparatus for measuring pressure, flow and arterial diameter, multichannel data aquisition equipment, equipment for data processing, analysis, plotting and stepper motor control using microcomputers, equipment for automated measurement of arterial smooth muscle mechanics in vitro and of microrheological properties of the arterial intima, and a special instrument that measures the effect of fluid shear on the arterial intima. There are two research microscopes, one inverted, with phase contrast. Most recently, apparatus has been built to measure the response of vascular cells to haemodynamic conditions in culture.

FUNDING in 1993 and 1994

CRC 	Cardiac Technology, Project 1.3  	Gow BS  	1993 	$30,200
								1994	*$15,000
(*committed to June 1994, with $35,400 requested for July 1994 to June 1995)

Total for 1993: $30,200

TEACHING in 1993

Dentistry 2

Course supervisor (1974-present)

Lectures: 18: 12, on cardiovascular physiology and 6, on respiration.

Practical classes: 3, each repeated 4 times, involving 1, of 3 h, on cardiovascular responses, 1, of 3 h, on human blood pressure, and 1, of 3 h, on respiration.

Tutorials: 3, each repeated to the 4 practical class groups, involving discussion of results, and 2 to the entire year on lecture material.

Examination: short answer and multiple choice questions.

Science 2

Lectures: 18: 12, on cardiovascular physiology and 6, on respiration. (Taken with Dentistry 2).

Practical classes: 3: 1, of 3 h, on cardiovascular responses, 1, of 3 h, on human blood pressure, and 1, of 3 h, on respiration.

Tutorials: 2, of 1 h.

Examination: as for Dentistry 2.

Science 2 Auxiliary

Lectures: 18: 12, on cardiovascular physiology and 6, on respiration. (Taken with Dentistry 2).

Examination: as for Dentistry 2.

Pharmacy 1

Lectures: 14, on cardiovascular physiology.

Examination: multiple choice questions (of the 5 alternatives, one correct, variety).

Medical Science 3/Science 3 (Cardiovascular)

Lectures: 7, on cardiovascular physiology.

Practical classes: 1, of 4 h, repeated, on cardiovascular physiology.

Site visit: 1, of 4h, to CSIRO.

Tutorials: 5, in which students presented and discussed a published scientific paper.

Examination: essay-type questions.

Other assessment conducted: practical reports and essay written during semester.

Postgraduate Teaching

Lectures: 8, to candidates in the Faculty of Anaesthetics (Part 1) on Cardiovascular Physiology.

Total distribution (hours of formal teaching)

				Dent2	Sci2	Pha1	SciAux	MedSc/Sc3	Total
Lectures			18	18*	14	18*	7		39
Practical classes (no.)		36(12)	9(3)	-	-	12(3)		59
Tutorials			12	3	1	-	5		21
(*Lectures to Dent2, Sci2 and SciAux were given concurrently)

Total formal contact teaching time = 119 h.

In addition time was spent in preparation of lectures, consultations by students, setting and marking exams and essays and course supervisor duties.

OTHER ACTIVITES in 1993

Community activity

President of the Dental Alumni Society.

5-YEAR RESEARCH PUBLICATIONS

JOURNAL ARTICLES

1989

Woodard J, Bertram CD, Gow BS (1989) The effect of radial position on volume measurements using a conductance catheter. Journal of Medicine, Biology, Engineering & Computing, 27, 25-32

Kukongviriyapan U, Gow BS (1989) Morphometric analysis of rabbit thoracic aorta after post-stenotic dilatation. Circulation Research, 65, 1774-86

1992

Gow BS, Legg MJ, Yu W, Kukongviriyapan U, Lee L (1992) Does vibration cause post-stenotic dilatation in vivo and influence atherogenesis in cholesterol-fed rabbits. Journal of Biomechanical Engineering,114, 20-25

Woodard J, Bertram CD, Gow BS (1992) Detecting right ventricular volume changes using the conductance catheter. Pacing and Clinical Electrophysiology, 15, 2283-2294

CHAPTER IN BOOK

Greenwald SE, Kukongviriyapan U, Gow BS (1990) The influence of vascular smooth muscle on the development of post-stenotic dilatation. Biomechanical Transport Processes, NATO ASI series, Mosora F, Caro CG, Scmid-Schönbein H, Pellissie R, Krause E, eds, Plenum Press, 347-356

CONFERENCE ABSTRACT AND PRESENTATION in 1993

Edwards N, Gow BS (1993) Rate of development of post-stenotic dilatation is dependent on endothelium. Proceedings of the Australian Physiological and Pharmacological Society, 24, 82P, Melbourne (Feb)