|
|
David Hui, Ph.D.
Price Schedule
|
Cardiovascular and Renal Function Core
|
The cardiovascular
and renal function core specializes in various blood pressure and flow parameters
that can be affected by diabetes and/or obesity in the intact animal or
isolated heart. In addition, we are capable of measuring changes in
arterial response to vessel wall injury. The core is directed by Dr.
David Hui.
|
|
|
|
Test Descriptions, References and Data
|
Test name:
|
Tail cuff pressure (C1001)
|
Keywords:
|
blood pressure, hypertension, nitric oxide
|
Description:
|
The measurement of systolic pressure through tail sphymmimanometry in the
mouse can be accomplished using computer controlled-pulse detection and data
acquisition. Minimal training period of 4 to 7 days and measurements
will be obtained over an extended period of 5 to 7 days. |
References:
|
Krege et al. (1995) A noninvasive computerized tail-cuff system for measuring
blood pressure in mice. Hypertension 25, 1111-1115. |
|
Test name:
|
Intra-arterial blood pressure measurements in the awake mouse (C1002)
|
Keywords:
|
blood pressure, hypertension, indwelling arterial catheter
|
Description:
|
This is a more precise blood pressure measurement than tail cuff pressure
method. Experiments and recording will be initiated at 24 to 48 hours
following implantation of indwelling arterial catheters. |
References:
|
Mattson, D.L. (1998) Long term measurement of arterial blood pressure in
conscious mice. Am. J. Physiol. 274, R564-R570. |
|
Test name:
|
Arterial baroreflex responses (C1003)
|
Keywords:
|
arterial baroreflex, vascular tone, cardiac function
|
Description:
|
Baroreflex is a homeostatic feedback mechanism whereby acute changes in
blood pressure result in compensatory alterations in cardiac function and
vascular tone. Resetting of the baroreflex can be an important hallmark
of cardiovascular dysfunction. |
References:
|
Merrill, D.C., Thompson, M.W., Carney, C.L., Granwehr, B.P., Schlager,
G., Robillard, J.E., and Sigmund, C.D. (1996) Chronic hypertension and altered
baroreflex responses in transgenic mice containing the human renin and human
angiotensinogen genes. J. Clin. Invest. 97, 1047-55. |
|
Test name:
|
Cardiac output (C1010)
|
Keywords:
|
pulse doppler flowmetry, cardiac output
|
Description:
|
Dose response relationships of blood pressure and ascending aorta blood
flow velocity will be determined for various vasoactive agents. Relative
changes in total peripheral resistance in closed-chest, anesthetized mice
will be evaluated with simultaneous measurements of arterial blood pressure
and cardiac output. |
References:
|
Hartley, C.J., Michael, L.H., and Entman, M.L. (1995) Noninvasive measurements
of ascending aortic blood velocity in mice. Am. J. Physiol. 268, H499-H505. |
|
Test name:
|
Regional blood flow measurements (C1011)
|
Keywords:
|
mesenteric blood flow, renal blood flow, hind limb blood flow
|
Description:
|
Transonic transit time flow probes will be used to provide high fidelity
volumetric flow measurements. |
References:
|
Lorenz, J.N., (2001) Considerations for the evaluation of renal function
in genetically engineered mice. Curr. Opin. Nephrol. Hypertens. 10,
65-69. |
|
Test name:
|
Arterial Response to Injury (Neointimal hyperplasia) (C1013)
|
Keywords:
|
neointimal hyperplasia, endothelial denudation, restenosis, angioplasty
|
Description:
|
Mouse carotid arteries will be denuded of the endothelium with a resin bead
derivatized catheter probe to mimic balloon angioplasty. Histological
sections will be made 14 days after arterial injury for measurement of neointimal
hyperplasia, medial size and thickness and vessel wall remodeling. |
References:
|
Zhu, B., Kuhel, D.G., Witte, D. and Hui, D.Y. (2000) Apolipoprotein E inhibits
neointimal hyperplasia after arterial injury in mice. Am. J. Pathol.
157, 1839-1848. |
|
Test name:
|
Vascular contractility (C1014)
|
Keywords:
|
vascular function, aortic ring, contractility
|
Description:
|
Isolated aorta preparations will be used to study vascular contractility.
Aorta will be precontracted with phenylephrine and exposed to increasing
concentrations of acetycholine. Isometric force will be measured to
determine endothelium-dependant response to stimulation. In addition,
spontaneous mechanical activity of the portal vein will be quantified in terms
of frequency, on-time, off-time, the tension-time integral and the maximum
positive and negative dF/dt. |
References:
|
Liu et. al (1997) Defective endothelium dependent relaxation of vascular
smooth muscle and endothelial cell Ca2+ signaling in mice lacking sarco(endo)plasmic
reticulum Ca-ATPase isoform 3. J. Biol. Chem. 272, 30538-30545. |
|
Test name:
|
Characterization of cardiac function in the isolated heart (C1020)
|
Keywords:
|
cardiac function, isolated heart, Langendorff, ex vivo, starling curves
|
Description:
|
Parameters measured: cardiac function (left ventricular pressure,
rates of contraction and relaxation, tau), heart rate, mean arterial pressure,
left atrial pressure, cardiac output, stroke volume, aortic and coronary
flow, myocardial oxygen consumption.
The research will employ an ex-vivo, isolated work-performing heart methodology
to study the fundamental contractile processes in the mouse heart.
Heart muscle function is analyzed through length-tension, pressure-volume,
and force frequency relationships of muscle, and the consequences of cardiac
performance to particular pathological stresses such as hypoxia and ischemia-reperfusion
injury can be assessed. All cardiovascular parameters are obtained
independently of any neuronal or hormonal influence.
|
References:
|
Book Chapter: Grupp IL, Schultz J, Syfris G, Grupp G. The
isolated work-performing and ejecting mouse heart preparation, comparison
and quantification of cardiac performance in transgenic and wild-type mice.
Cardiovascular physiology in the genetically engineered mouse, 2nd
ed. Hoit BD, Walsh RA, eds. Boston: Kluwer Academic Publishers,
2001 pp. 129-150.
|
|
Test name:
|
Echocardiography (C1021)
|
Keywords:
|
echocardiography, myocardial performance, ventricular function
|
Description:
|
Transthoracic echocardiography will be used as index of myocardial performance.
M-mode and pulsed-Doppler echocardiography will be used for noninvasive
assessment of ventricular function. Left ventricular function will be
determined under baseline conditions and during beta-adrenergic stimulation.
Data to be collected include: left ventricular end-diastole and systole,
septal wall thickness at end diastole, posterior wall thickness ar end diastole,
pressure gradient from ascending and descending aortic flow velocities, heart
rate, stroke volume and cardiac output. |
References:
|
Hoit, B.D., Shoury, S.F., Kranias, E.G., Ball,N. and Walsh, R.A. (1995)
In vivo echocardiographic detection of enhanced left ventricular function
in gene targeted mice with phospholambin deficiency. |
|
Test name:
|
Left ventricular functions of the heart (C1022)
|
Keywords:
|
left ventricles, cardiac contractility, electrical pacing, isolated
heart
|
Description:
|
Ventricular pressure measurements will be made in intact animals as
follows: cardiovascular performance in response to beta-adrenergic
stimulation will be evaluated by infusing isoproterenol, with continuous
monitoring of blood pressure wave. More precise evaluation of cardiac
contractility may be made by combining left ventricular pressure measurements
with M-mode echocardiography to obtain pressure-dimension relationships.
Additional studies may be extended to directly assess cardiac functions
using isolated work-performing heart preparations. |
References:
|
Lorenz, J.N. and Kranias, E.G. (1997) Cardiac function in intact
phspholamban-deficient and heterozygous mice. Am. J. Physiol. 273,
H2826-H2831.
Grupp, I.L., Subramaniam, A., Hewitt, T.E., Robbins, J., and Grupp, G.
(1993) Comparison of normal, hypodynamic, and hyperdynamic mouse hearts
using isolated work performing preparations. Am. J. Physiol. 265,
H1401-H1410.
|
|
Test name:
|
Micropuncture measurements (C1030)
|
Keywords:
|
micropuncture measurements of renal function
|
Description:
|
Animals will receive a priming dose and maintenance infusion of FITC-inulin.
Proximal and distal convolution of several surface nephrons will be
identified and mapped by intraluminal injection of a small volume of dye.
Late proximal puncture sites will be identified as the last surface
segment to fill with the dye. Early distal puncture sites can be identified
when the dye returns to the kidney surface. |
References:
|
Lorenz, J.N. and Gruenstein, R. (1999) A simple, nonradioactive method for
evaluating single nephron filtration rate using FITC-inulin. Am. J. Physiol.
276, F172-F177.
|
|
Test name:
|
Renal Blood Flow Regulation (Free flow measurements)(C1031)
|
Keywords:
|
renal function, free flow
|
Description:
|
After identification of proximal and distal puncture sites, an oil block
will be introduced and a complete tubular fluid sample will be collected.
In those nephrons which have both proximal and distal convolutions,
collections will be made from the distal site prior to the proximal site.
When the same nephrons are re-punctured during the second experimental period,
disappearance of the original oil block and normal fluid flow at the distal
site will be used as verification of tubule patency. Tubular fluid samples
will be obtained to measure Na+ and CL- and FITC-inulin concentrations. |
References:
|
Lorenz, J.N. and Gruenstein, R. (1999) A simple, nonradioactive method for
evaluating single nephron filtration rate using FITC-inulin. Am. J.
Physiol. 276, F172-F177. |
|
Test name:
|
In situ microperfusion (C1032)
|
Keywords:
|
microperfusion, kidney functions
|
Description:
|
Early and late convolutions of a single proximal tubule having 3-5 loops
on the kidney surface will be identified and mapped as described for other
renal function tests. In a small population of nephrons, late proximal
and early distal convolutions from a single nephron will ne identified for
microperfusion of the loop segment. |
References:
|
Lorenz, J.N., Schultheis, P.J., Shull, G. and Schnermann, J. (1999) Micropuncture
analysis of single nephron function in NHE3 deficient mice. Am. J. Physiol.
276, F447-F453. |
|
Test name:
|
Control of renal perfusion pressure (C1033)
|
Keywords:
|
pressure natriuresis response
|
Description:
|
Hormones that influence renal function will be infused to produce a slight
diuresis that permits sufficient urine collection for evaluation of pressure
natriuresis responses. |
References:
|
Lorenz., J.N. and Gruenstein, R. (1999) A simple, nonradioactive method
for evaluating single nephron filtration rate using FITC-inulin. Am. J. Physiol.
276, F172-F177. |
|
Test name:
|
Whole kidney clearance (C1034)
|
Keywords:
|
renal blood pressure, glomerular filtration rate, ion secretion, plasma
concentrations, urine concentrations
|
Description:
|
Standard clearance techniques will be used to evaluate renal blood pressure,
glomerular filtration rate and excretion of sodium, potassium and chloride
ions. Sodium and potassium concentrations will be measured in 4 microL
plasma or urine by flame photometry. Chloride will be measured by chloridometer.
Osmolality will be measured by freezing point depression. |
References:
|
Lorenz., J.N., and Gruenstein, R. (1999) A simple, nonradioactive method
for evaluating single nephron filtration rate using FITC-inulin. Am.
J. Physiol. 276, F172-F177. |
|
|
|
