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Hemodynamic response to OKT3 in orthotopic heart transplant recipients: evidence for reversible myocardial
W M Breisblatt1, D S Schulman, K Stein
1Department of Anesthesiology/Critical Care Medicine, Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pa.
The murine-derived monoclonal antibody OKT3 has been shown to be a useful immunosuppressive agent in transplant recipients; but it may cause cardiac instability and hemodynamic findings similar to those seen in septic shock after a first dose. Eight patients who received orthotopic heart transplants and were randomized to OKT3 therapy for immunosuppression were evaluated with serial hemodynamic and radionuclide monitoring for an 8-hour period during the first dose of OKT3. Cytokines including tumor necrosis factor-alpha, interleukin-1 and -2, and interferon-gamma were measured hourly to determine the potential mechanism of action of OKT3. All patients tolerated OKT3, although most had symptoms--pyrexia, chills, dyspnea, nausea and vomiting, and fever--within an hour after the dose. All patients exhibited a biphasic hemodynamic response to the first dose of OKT3. The initial hemodynamic response was characterized by a hyperdynamic phase with involvement in cardiac function as measured by cardiac output and ejection fraction. Left ventricular ejection fraction increased from 68% +/- 10% to 79 +/- 11% and was accompanied by increases in right ventricular ejection fraction and increases in cardiac index from 2.1 +/- 1.1 to 3.8 +/- 1.3 L/min/m2. The increase in ejection fraction was accompanied by a significant decrease in systemic vascular resistance index, from 2190 +/- 740 to 1608 +/- 573 dyne.sec.cm-5. The improvement in left ventricular ejection was caused by a significant decrease in end-systolic volume index (18 +/- 9.5 to 11 +/- 7 ml/m2). This occurred within the first 2 hours after OKT3 and was followed by cardiac index and ejection fraction returning to baseline in the next 2 to 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
The murine-derived monoclonal antibody OKT3 has been shown to be a useful immunosuppressive agent in transplant recipients; but it may cause cardiac instability and hemodynamic findings similar to those seen in septic shock after a first dose. Eight patients who received orthotopic heart transplants and were randomized to OKT3 therapy for immunosuppression were evaluated with serial hemodynamic and radionuclide monitoring for an 8-hour period during the first dose of OKT3. Cytokines including tumor necrosis factor-alpha, interleukin-1 and -2, and interferon-gamma were measured hourly to determine the potential mechanism of action of OKT3. All patients tolerated OKT3, although most had symptoms--pyrexia, chills, dyspnea, nausea and vomiting, and fever--within an hour after the dose. All patients exhibited a biphasic hemodynamic response to the first dose of OKT3. The initial hemodynamic response was characterized by a hyperdynamic phase with involvement in cardiac function as measured by cardiac output and ejection fraction. Left ventricular ejection fraction increased from 68% +/- 10% to 79 +/- 11% and was accompanied by increases in right ventricular ejection fraction and increases in cardiac index from 2.1 +/- 1.1 to 3.8 +/- 1.3 L/min/m2. The increase in ejection fraction was accompanied by a significant decrease in systemic vascular resistance index, from 2190 +/- 740 to 1608 +/- 573 dyne.sec.cm-5. The improvement in left ventricular ejection was caused by a significant decrease in end-systolic volume index (18 +/- 9.5 to 11 +/- 7 ml/m2). This occurred within the first 2 hours after OKT3 and was followed by cardiac index and ejection fraction returning to baseline in the next 2 to 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)