Endothelial cell dysfunction and nitric oxide synthase

pass graft surgery. Her medical history revealed coronary artery disease, a coronary artery bypass graft four years ago, hypertension, hypothyroidism, a right below-the-knee amputation two years ago, and a left toe amputation one year ago. Last year she underwent left femoral-popliteal bypass graft surgery; during the past four years, she has had recurrent arteriovenous graft failure necessitating six additional revascularization procedures. Physical examination revealed a slightly obese woman who was somewhat short of breath at rest but in no apparent distress. Her temperature was 97.78F; heart rate, 87 beats/min; respiratory rate, 18 breaths/min; and blood pressure, 118/78 mm Hg. No jugular venous distention was present. She had a grade II/VI systolic ejection murmur. Four toes on her left foot were gangrenous; a large open ulcer was present. The left dorsalis pedis pulse was weak. CASE PRESENTATIONS Her medications included: human insulin (recombinant DNA Patient 1 origin, Humulin N), 20 units subcutaneously every morning; A 63-year-old lawyer who had devoted most of his life to calcium acetate, 1320 mg 3 times daily; digoxin, 0.125 mg orally politics was found at age 50 to have an elevated blood pressure every other day; erythropoietin a, 5000 units subcutaneously (140/100 mm Hg), left-ventricular hypertrophy, and nonspecific every other day; levothyroxine sodium, 0.75 mg daily; enalapril, T-wave changes on his electrocardiogram (EKG). He had had 5 mg daily; pravastatin, 20 mg daily; warfarin, 2.5 to 5.0 mg, typhoid fever at age 30 and poliomyelitis at age 39; the latter as needed to maintain INR at 2.0 to 2.5; and multivitamins. had resulted in waist weakness and paralysis of his legs. Despite Laboratory data on admission included: glucose (measured his paralysis, he maintained a busy work and social schedule. by finger sticks), 166 to 188 mg/dL; hematocrit, 35.6%; albumin, In his late 50s, he began to complain periodically of “drawing 3.0 g/dL; total calcium, 8.2 mg/dL; inorganic phosphorus, 3.6 a blank”; the symptom probably was due to transient ischemic mg/dL; digoxin, 0.6 ng/mL; cholesterol, 180; triglycerides, 129; attacks. At age 62, he was examined by several physicians. The HDL, 22; LDL cholesterol, 118 mg/dL; ferritin, 526 ng/mL; records show that an apical impulse was palpable in the anterior and PTH, 99.9 pg/mL. The EKG was significant for Q-waves axillary line, and his blood pressure was 180/100 mm Hg, but in leads III and AVR and nonspecific T-wave changes, with neither an EKG nor a urinalysis was performed. A digitalis no interval changes from the record three months earlier. preparation was prescribed, but not nitroglycerin. A few months A two-dimensional echocardiogram performed two years before his death, he was described as “puffy,” was found to ago showed normal global left-ventricular systolic function, have cardiomegaly and hepatomegaly, and was noted to be left-ventricular hypertrophy, aortic stenosis, and left atrial enirritable and somnolent. A few months later, while the patient largement. Angiography revealed moderate, diffuse atherowas vacationing, he experienced the abrupt onset of headache, sclerotic aorto-iliac disease bilaterally; the left femoral-to-popfainted, and died within two hours. liteal bypass graft was totally occluded. Her left profunda femoralis was severely diseased, and the left superficial femoral Patient 2 artery was occluded. The patient tolerated the angiographic proA 73-year-old woman with end-stage renal disease had been cedure well, and a below-the-knee amputation was scheduled. treated with hemodialysis for the past nine years. She had had non-insulin-dependent diabetes mellitus for 40 years. She was admitted to the hospital for possible left femoral-popliteal byDISCUSSION