Cardiopulmonary toxicity in patients with breast carcinoma during plasma perfusion over immobilized protein A. Pathophysiology of reaction and attenuating methods.
Tumoricidal reactions in dogs with spontaneous breast carcinoma occur after perfusion of plasma over protein A derived from Staphylococcus aureus and immobilized in collodion charcoal. When this treatment was extended to humans with breast cancer, hemodynamic and physiologic changes were noted. The evolution and spectrum of these reactions were evaluated during 47 plasma infusions in five patients. Initial treatment conditions consisting of rapid perfusion of plasma over high quantities of immobilized protein A were employed for 12 treatments in two patients. Within 30 minutes after treatments were begun, mean blood pressure, systemic vascular resistance, and stroke volume increased, as did heart rate, cardiac output, and rectal temperature; however, mean pulmonary artery pressure and total pulmonary resistance did not change. At 90 minutes, hypotension developed (lowest mean blood pressure was 59 +/- 14 mm Hg) that was associated with a decrease in systemic vascular resistance and total pulmonary resistance (536 +/- 66 and 146 +/- 44 dynes . second . cm-5, respectively). Cardiac output increased, tachycardia developed, stroke volume decreased, and rectal temperature increased. During the hypotensive phase, values of creatinine clearance and fractional excretion of sodium diminished. Noncardiogenic pulmonary edema appeared occasionally, with bronchospasm noted once. No hemodynamic changes were seen when saline solution was passaged over protein A immobilized in collodion charcoal or when autologous plasma was given without passage over protein A immobilized in collodion charcoal. Treatment conditions were modified by diminishing protein A quantity and plasma volume and slowing plasma perfusion rate, which resulted in significant attenuation of all cardiopulmonary responses. This report, then, defines for the first time the physiologic basis of the cardiopulmonary toxicity in humans after plasma perfusion over immobilized protein A.
D001943:Breast Neoplasms / Q000503:physiopathology / Q000628:therapy*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007022:Hypotension / Q000209:etiology*; D007677:Kidney Function Tests; D008168:Lung / Q000503:physiopathology*; D010949:Plasma; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000209:etiology; D013205:Staphylococcal Protein A / Q000008:administration & dosage*; D014655:Vascular Resistance; D014664:Vasodilation
D013205:Staphylococcal Protein A