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Cardiovascular adaptation to orthostatic stress during vasodilator therapy
Author(s) -
Lipsitz Lewis A.,
Connelly Carolyn M.,
KelleyGag Margaret,
Kiely Dan K.,
Abernethy Darrell,
Waksmonski Carol
Publication year - 1996
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(96)90203-9
Subject(s) - medicine , nicardipine , isosorbide dinitrate , blood pressure , cardiology , orthostatic vital signs , vascular resistance , vasodilation , anesthesia , heart rate , coronary artery disease
Background Orthostatic hypotension is a dangerous problem in elderly patients, often exacerbated by vasodilator medications. Age‐ and disease‐related impairments in cardioacceleration and diastolic ventricular function may make older patients particularly vulnerable to the hypotensive effects of these drugs. Therefore we aimed to determine mechanisms of postural blood pressure regulation in elderly patients with coronary artery disease and to compare the effects of isosorbide dinitrate and nicardipine hydrochloride on postural blood pressure homeostasis in these patients. Methods Twenty elderly subjects with stable coronary artery disease (age, 76 ± 4 [SD] years) underwent a baseline evaluation followed by a double‐blind, randomized crossover comparison of nicardipine (20 mg by mouth t.i.d.) versus isosorbide (20 mg by mouth t.i.d.). Doppler echocardiography and a 15‐minute 60‐degree head‐up tilt test were conducted on no study medications and then after successive 3‐week treatment periods with nicardipine or isosorbide. Blood pressure, heart rate, vascular resistance, cardiac output, and spectral characteristics of heart rate and blood pressure variability were measured before and during each tilt. Results Isosorbide treatment was associated with a higher prevalence of symptoms of cerebral hypoperfusion and a failure to increase systemic vascular resistance during tilt. While taking isosorbide subjects were able to preserve cardiac output and maintain upright blood pressure through enhanced cardioacceleration. During nicardipine treatment systemic vascular resistance and low‐frequency blood pressure variability were reduced, but the ability to increase systemic vascular resistance during tilt was preserved. Conclusions Although nicardipine may decrease vascular responsiveness to sympathetic activation, the baroreflex‐mediated vasoconstrictor response to upright tilt remains intact. In contrast, isosorbide impairs the systemic vascular response to orthostatic stress in elderly patients with stable coronary artery disease. Clinical Pharmacology & Therapeutics (1996) 60 , 461–471; doi: