Hemodynamic response to OKT3 in orthotopic heart transplant recipients: evidence for reversible myocardial dysfunction.

Abstract

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)

• Authors: W M Breisblatt, D S Schulman, K Stein, C J Wolfe, T Whiteside, R Kormos, R L Hardesty
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) 1991 May-Jun Vol. 10 Issue 3 Pg. 359-65 ISSN: 1053-2498 [Print] United States
• PMID: 1906745 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal
• Muromonab-CD3
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Antibodies, Monoclonal (therapeutic use)
• Female
• Graft Rejection (immunology)
• Heart (diagnostic imaging)
• Heart Transplantation (immunology, physiology)
• Hemodynamics (physiology)
• Humans
• Immunosuppression Therapy
• Male
• Muromonab-CD3
• Radionuclide Imaging
• Tumor Necrosis Factor-alpha (analysis)
• Ventricular Function (physiology)