ABSTRACT
Familial hypercholesterolemia (FH), a genetic disease characterized by increased levels of total and low-density lipoprotein cholesterol in the blood, results in a markedly increased incidence of atherosclerosis and coronary artery disease in homozygotes and to a lesser extent in heterozygotes. The purpose of this study was to detect the presence of myocardial ischemia, particularly in heterozygotes, with stress single-photon emission computed tomography thallium-201 scanning and to determine if there were any differentiating variables between heterozygotes with normal and abnormal thallium-201 scans. Fifty-four patients (mean age 16 years; range 8 to 24) with FH were analyzed (4 homozygotes and 50 heterozygotes). Eleven heterozygotes and 3 homozygotes had abnormal thallium-201 scans. Family history, lipid profile, age and sex of heterozygotes with FH did not predict the presence of myocardial ischemia. The mean total cholesterol level in heterozygotes with normal thallium-201 scans was 7.68 +/- 2.29 mmol/liter (297 mg/dl), which was not significantly different from that in heterozygotes with abnormal scans (7.63 +/- 1.07 mmol/liter [295 mg/dl]; p = 0.91). The coronary angiography of 1 homozygote who had an abnormal thallium-201 scan demonstrated a 50% stenosis of the left anterior descending artery. Aggressive, repetitive plasma exchange was then instituted. The 11 heterozygotes with abnormal thallium-201 scans underwent more rigorous dietary and drug therapy. It is concluded that myocardial ischemia with stress in heterozygotes with FH can occur at a young age and that thallium-201 scanning should be performed early as a screening test and to guide patient management.
Subject(s)
Coronary Disease/diagnostic imaging , Hyperlipoproteinemia Type II/complications , Thallium Radioisotopes , Tomography, Emission-Computed, Single-Photon , Adolescent , Adult , Age Factors , Child , Coronary Disease/etiology , Coronary Disease/genetics , Exercise Test , Female , Heterozygote , Humans , Male , Medical History TakingABSTRACT
We directly measured the net pulmonary extraction of circulating norepinephrine, epinephrine and dopamine in control patients and patients with primary or secondary pulmonary hypertension. Mixed pulmonary artery norepinephrine, epinephrine and dopamine were 314 +/- 13 pg/ml, 102 +/- 9 pg/ml, 51 +/- 5 pg/ml, respectively, for the control group; values were similar in patients with pulmonary hypertension. The pulmonary extraction of norepinephrine was 25.4 +/- 2.6% (clearance 266 +/- 62 ng/min) in control patients; epinephrine and dopamine were not extracted. There was no net extraction or production of any of the three catecholamines by the lungs in any of the patients with pulmonary hypertension. We conclude that the lungs play a significant role in the inactivation of circulating norepinephrine in man. This metabolic function of the lungs appear to be lost in pulmonary hypertension.
Subject(s)
Catecholamines/metabolism , Hypertension, Pulmonary/metabolism , Lung/metabolism , Adult , Aged , Dopamine/metabolism , Epinephrine/metabolism , Heart Diseases/physiopathology , Humans , Hypertension, Pulmonary/physiopathology , Middle Aged , Norepinephrine/metabolism , Pulmonary Circulation , Vascular ResistanceABSTRACT
We measured aortic and coronary sinus dopamine (DA), epinephrine (E), and norepinephrine (NE) in eight patients with cardiac ischemia (I) and eight control subjects (C). Samples were taken at rest (73 +/- 3 beats/min in C and 68 +/- 3 beats/min in I) and during coronary sinus pacing to peak rates (144 +/- 4 beats/min in C and 136 +/- 6 beats/min in I). Arterial NE was higher in the ischemic patients at rest (254 +/- 25 pg/ml in C and 324 +/- 21 in I; p less than 0.05). There were no differences in arterial E and DA. Neither pacing nor angina affected peripheral catecholamine concentrations. Resting myocardial NE flux was similar for both groups. With pacing, coronary sinus flow and net myocardial NE release increased significantly in both groups. The maximum relative increase in net myocardial NE release was less in the ischemic patients than in the controls (575 +/- 145% in C and 255 +/- 40% in I; p less than 0.05). Thus, angina induced by pacing does not augment peripheral sympathetic activity. Furthermore, pacing-induced angina appears to be associated with a decrease in cardiac sympathetic tone compared with that found in paced controls.
