Abstract

The unifying hypothesis of this investigation is that the progressive increase in regurgitant volume in patients with long-term MR stimulates activation of the sympathetic nervous system (SNS) as a compensatory mechanism to maintain effective forward output, arterial pressure, and tissue perfusion. This compensatory mechanism affects a decrease in beta AR responsiveness resulting in LV contractile dysfunction. It follows, therefore, that treatment with mitral valve surgery will restore LV contractile function to the extent that SNS activity is diminished and beta AR responsiveness is restored. Preliminary studies in five patients have demonstrated a relationship between regurgitant volume and adenylyl cyclase activity (r=0.86) and contractile function (r=0.75). Similarly, correlatal plasma norepinephrine levels and adenylyl cyclase activity reserved with contractile function (r=0.91 & 0.65). Thus, preliminary data support the hypothesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000042-37
Application #
6244518
Study Section
Project Start
1997-02-20
Project End
1997-11-30
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
37
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Robarge, Jason D; Desta, Zereunesay; Nguyen, Anne T et al. (2017) Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer. Breast Cancer Res Treat 161:453-461
Crane, Natania A; Jenkins, Lisanne M; Bhaumik, Runa et al. (2017) Multidimensional prediction of treatment response to antidepressants with cognitive control and functional MRI. Brain 140:472-486
Hertz, Daniel L; Speth, Kelly A; Kidwell, Kelley M et al. (2017) Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients. Breast Cancer Res Treat 165:659-668
Hertz, D L; Kidwell, K M; Seewald, N J et al. (2017) Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in postmenopausal patients with breast cancer. Pharmacogenomics J 17:521-527
Kadakia, Kunal C; Kidwell, Kelley M; Seewald, Nicholas J et al. (2017) Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors. Breast Cancer Res Treat 164:411-419
Spengler, Erin K; Kleiner, David E; Fontana, Robert J (2017) Vemurafenib-induced granulomatous hepatitis. Hepatology 65:745-748
Heidemann, Lauren; Law, James; Fontana, Robert J (2017) A Text Searching Tool to Identify Patients with Idiosyncratic Drug-Induced Liver Injury. Dig Dis Sci 62:615-625
As-Sanie, Sawsan; Kim, Jieun; Schmidt-Wilcke, Tobias et al. (2016) Functional Connectivity is Associated With Altered Brain Chemistry in Women With Endometriosis-Associated Chronic Pelvic Pain. J Pain 17:1-13
Hertz, Daniel L; Henry, N Lynn; Kidwell, Kelley M et al. (2016) ESR1 and PGR polymorphisms are associated with estrogen and progesterone receptor expression in breast tumors. Physiol Genomics 48:688-98
Mehta, Rupal; Cai, Xuan; Lee, Jungwha et al. (2016) Association of Fibroblast Growth Factor 23 With Atrial Fibrillation in Chronic Kidney Disease, From the Chronic Renal Insufficiency Cohort Study. JAMA Cardiol 1:548-56

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