Submitted on January 7, 2003
Accepted on April 1, 2004
Cardiac-Specific Norepinephrine Mass Transport and its Relationship to Left Ventricular Size and Systolic Performance
P. Michael Grossman1, Oscar A. Linares2, Mark A. Supiano3, Hakan Oral4, Rajendra H. Mehta1, and Mark R. Starling1*
1 Divisions of Cardiology, University of Michigan Healthcare System, Ann Arbor, MI, USA; The Geriatric Research Education and Clinical Center and Cradiology Section, The Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA
2 Department of Internal Medicine, and the Horace H. Rackham School of Graudate Studies, University of Michigan, Ann Arbor, MI, USA
3 Department of Geriatric Medicine, University of Michigan Healthcare System, Ann Arbor, MI, USA; The Geriatric Research Education and Clinical Center and Cradiology Section, The Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA
4 Divisions of Cardiology, University of Michigan Healthcare System, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: mrstar{at}umich.edu.
The objective of this study was to develop a technique for quantifying cardiac-specific norepinephrine (NE) mass transport and to determine whether cardiac NE kinetic modeling parameters were related to the physiologic variables of left ventricular (LV) size and systolic performance in nine patients with chronic mitral regurgitation (MR). Biplane contrast cineventriculograms were used to determine LV size and ejection fraction, micromanometer LV pressures and radionuclide LV volumes from a range of loading conditions were used to calculate LV end-systolic elastance (Ees), and [3H]-NE infusions with LV and coronary sinus sampling for [3H]-NE and endogenous NE during and after termination of the infusions were used to model NE mass transport. The total NE release rate into the cardiac interstitial fluid (MRIF ) averaged 859±214 pmol/min, and NE that was released de novo into the cardiac interstitial fluid (Mu,re,enIF) averaged 546±174 pmol/min. Both the and MRIF and M u,r,enIF values correlated directly with LV end-systolic volume (r=0.84, p=0.005 and r=0.86, p=0.003); inversely with LV ejection fractions (r=-0.75, p=0.02 and r=-0.81, p=0.008); and in an inverse fashion with LV end-systolic elastance values, which was optimally fit by a non-linear function (r=0.89, p=0.04 and r=0.96, p=0.01). We conclude that total and newly released NE into the interstitial fluid of the heart determined using a regional mass transport kinetic model are specific measures of regional cardiac-specific SNS activity and are strongly related to measures of LV size and systolic performance. These data support the concept that this new model of organ-specific NE kinetics has physiologic relevance.
