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CLINICAL STUDIES

Effects of therapy with nifedipine GITS or atenolol on mental stress-induced ischemic left ventricular dysfunction

Thomas C. Andrews, MD, FACC^*, John D. Parker, MD, FACC, Sue Jacobs, PhD, Richard Friedman, PhD, Nancy Cummings, RN^||, Gail MacCallum, BS^¶, Finn Mannting, MD^{# **}, Geoffrey H. Tofler, MD, FACC^** , William Carlson, MD, FACC^{¶ **}, James E. Muller, MD, FACC and Peter H. Stone, MD, FACC^{¶ **}

^* Department of Internal Medicine, Cardiology Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Division of Cardiology, Mount Sinai Hospital, University of Toronto, Toronto, Canada
Department of Counseling, University of North Dakota, Grand Forks, North Dakota, USA
Department of Psychiatry, State University of New York at Stony Brook, USA
^|| Department of Surgery, Brigham and Women’s Hospital, Boston, Massachusetts, USA
^¶ Cardiovascular Division/Department of Medicine, Brigham and Women’s Hospital, Boston, USA
^# Department of Nuclear Medicine, Brigham and Women’s Hospital, Boston, USA
^** Harvard Medical School, Boston, USA
Institute for Prevention of Cardiovascular Disease, Deaconess Hospital, Boston, USA
Division of Cardiovascular Medicine, University of Kentucky, Louisville, Kentucky, USA

Manuscript received August 5, 1997; revised manuscript received July 1, 1998, accepted July 24, 1998.

Address for correspondence: Dr. Peter H. Stone, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115

Objectives. We sought to determine the effect of nifedipine gastrointestinal therapeutic system (GITS) or atenolol on ischemic left ventricular dysfunction induced by mental stress.

Background. The efficacy of conventional antianginal therapy in preventing myocardial ischemia induced by mental stress is unknown.

Methods. Nifedipine GITS, atenolol and placebo were administered to 15 subjects with stable angina in a double-blind crossover trial. Subjects underwent a series of mental stressors at the end of each treatment. Radionuclide ventriculography was performed at baseline and at peak mental stress. Other measured variables included time to ischemia on exercise treadmill testing, ischemia on 48-h ambulatory electrocardiogram (ECG) monitoring, and resting and mental stress-induced levels of plasma catecholamines, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and platelet aggregability.

Results. Mental stress resulted in a significant increase in plasma epinephrine and norepinephrine levels during each treatment phase. Atenolol therapy was associated with lower baseline and postmental stress rate-pressure product compared with nifedipine or placebo. Therapy with either nifedipine GITS or atenolol prevented the development of wall-motion abnormalities and the decline in regional ejection fraction (EF) in the segment with the largest deterioration in wall motion during placebo therapy. Both medications prevented the decrease in global EF in subjects who demonstrated at least a 5% fall in global EF on placebo therapy. No therapy exerted a statistically significant benefit on exercise performance or frequency of ischemia during ambulatory ECG monitoring.

Conclusions. Both nifedipine GITS and atenolol are effective at preventing mental stress-induced wall-motion abnormalities, although the mechanisms may be different.

Abbreviations and Acronyms   ADP = adenosine diphosphate   AECG = ambulatory electrocardiography   ECG = electrocardiogram   EDV = end diastolic volume   EF = ejection fraction   ESV = end systolic volume   NYHA = New York Heart Association   PAI-1 = plasminogen activator inhibitor-1   SV = stroke volume   tPA = tissue plasminogen activator

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