From the Department of Surgery, Division of Cardiovascular and Thoracic
Surgery, Duke University Medical Center, Durham, NC.
Background—Right
ventricular (RV) hypertrophy is an adaptive
process that occurs in the setting of chronic pulmonary
hypertension (CPH) and can lead to alterations in normal RV
diastolic properties. This study was designed to
investigate the effects of NO and milrinone on RV diastolic
dysfunction in the setting of CPH and RV hypertrophy by use
of a canine model of monocrotaline pyrrole (MCTP)–induced
CPH.
Methods and Results—Sixteen mongrel dogs (22 to 24 kg) were used.
Animals underwent percutaneous pulmonary artery
(PA) catheterization to measure pulmonary
hemodynamics before and 8 weeks after injection of 3
mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after
injection, all hearts were instrumented with a PA flow probe,
sonomicrometric dimension transducers, and
micromanometers. Data were collected at baseline
and after both NO and milrinone administration. Diastolic
properties were quantified by use of the end-diastolic
pressure-volume relationship and the time constant of
ventricular isovolumic relaxation. Eight weeks after
injection, significant increases in the PA pressure and
pulmonary vascular resistance were observed in MCTP dogs.
Significant worsening of RV diastolic function occurred in
association with significant increases in the ratio of RV dry weight to
LV+septal dry weight. NO and milrinone administration both led to
significant improvements in RV diastolic properties.
Conclusions—In the setting of MCTP-induced CPH, significant
worsening of RV diastolic function was observed in
association with significant increases in the ratio of RV dry weight to
LV+septal dry weight, suggesting that these changes are partially due
to RV hypertrophy. The significant improvement in RV
diastolic properties after both NO and milrinone administration
suggests that these agents may be effective forms of pharmacological
therapy for improving RV diastolic dysfunction in the
setting of CPH.
© 1998 American Heart Association, Inc.
Basic Science Reports
Pharmacological Strategies for Improving Diastolic Dysfunction in the Setting of Chronic Pulmonary Hypertension
Key Words: hypertension, pulmonary • diastole • ventricles • hypertrophy
This article has been cited by other articles:
 |
|
 |
|
  L. P. Badano, C. Ginghina, J. Easaw, D. Muraru, M. T. Grillo, P. Lancellotti, B. Pinamonti, G. Coghlan, M. P. Marra, B. A. Popescu, et al. Right ventricle in pulmonary arterial hypertension: haemodynamics, structural changes, imaging, and proposal of a study protocol aimed to assess remodelling and treatment effects Eur J Echocardiogr, October 7, 2009; (2009) jep152v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Kawut, N. Al-Naamani, C. Agerstrand, E. Berman Rosenzweig, C. Rowan, R. J. Barst, S. Bergmann, and E. M. Horn Determinants of Right Ventricular Ejection Fraction in Pulmonary Arterial Hypertension Chest, March 1, 2009; 135(3): 752 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zierer, S. J. Melby, R. K. Voeller, and M. R. Moon Interatrial shunt for chronic pulmonary hypertension: differential impact of low-flow vs. high-flow shunting Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H639 - H644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T.-J. Gan, S. Holverda, J. T. Marcus, W. J. Paulus, K. M. Marques, J. G.F. Bronzwaer, J. W. Twisk, A. Boonstra, P. E. Postmus, and A. Vonk-Noordegraaf Right Ventricular Diastolic Dysfunction and the Acute Effects of Sildenafil in Pulmonary Hypertension Patients Chest, July 1, 2007; 132(1): 11 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Denault, Y. Lamarche, P. Couture, F. Haddad, J. Lambert, J.-C. Tardif, and L. P. Perrault Inhaled milrinone: a new alternative in cardiac surgery? Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2006; 10(4): 346 - 360. [Abstract] [PDF]
|
|
|
|
 |
|
 N. F. Voelkel, R. A. Quaife, L. A. Leinwand, R. J. Barst, M. D. McGoon, D. R. Meldrum, J. Dupuis, C. S. Long, L. J. Rubin, F. W. Smart, et al. Right Ventricular Function and Failure: Report of a National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure Circulation, October 24, 2006; 114(17): 1883 - 1891. [Full Text] [PDF]
|
|
|
|
|
|
S. L. Gaynor, H. S. Maniar, J. B. Bloch, P. Steendijk, and M. R. Moon Right Atrial and Ventricular Adaptation to Chronic Right Ventricular Pressure Overload Circulation, August 30, 2005; 112(9_suppl): I-212 - I-218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. J. Leeuwenburgh, P. Steendijk, W. A. Helbing, and J. Baan Indexes of diastolic RV function: load dependence and changes after chronic RV pressure overload in lambs Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1350 - H1358. [Abstract] [Full Text] [PDF]
|
|