CARDIOVASCULAR ADAPTATION TO ORTHOSTATIC STRESS DURING VASODILATOR THERAPY

Background: Orthostatic hypotension is a dangerous problem in elderly patients, often exacerbated by vasodilator medications, Age- and disea se-related impairments in cardioacceleration and diastolic ventricular function may make older patients particularly vulnerable to the hypot ensive effects of these drugs, Therefore we aimed to determine mechani sms of postural blood pressure regulation in elderly patients with cor onary artery disease and to compare the effects of isosorbide dinitrat e and nicardipine hydrochloride on postural blood pressure homeostasis in these patients. Methods: Twenty elderly subjects with stable coron ary artery disease (age, 76+/-4 [SD] years) underwent a baseline evalu ation followed by a double-blind, randomized crossover comparison of n icardipine (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 til t test were conducted on no study medications and then after successiv e a-week treatment periods with nicardipine or isosorbide, Blood press ure, heart rate, vascular resistance, cardiac output, and spectral cha racteristics of heart rate and blood pressure variability were measure d before and during each tilt. Results: Isosorbide treatment was assoc iated with a higher prevalence of symptoms of cerebral hypoperfusion a nd a failure to increase systemic vascular resistance during tilt. Whi le 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-freq uency blood pressure variability were reduced, but the ability to incr ease systemic vascular resistance during tilt was preserved. Conclusio ns: Although nicardipine may decrease vascular responsiveness to sympa thetic activation, the baroreflex-mediated vasoconstrictor response to upright tilt remains intact, In contrast, isosorbide impairs the syst emic vascular response to orthostatic stress in elderly patients with stable coronary artery disease.