Plasmapheresis with intravenous immunoglobulin G is effective in patients with elevated panel reactive antibody prior to cardiac transplantation.

BACKGROUND: Patients with a PRA >10% are considered to be at greater risk for the development of not only acute cellular and humoral rejection but also increased mortality when compared to nonsensitized patients following transplantation. All patients with a PRA >10% at our institution are treated with plasmapheresis and intravenous immunoglobulin G immediately prior to cardiac transplantation. METHODS: Sixteen (Group 1) of 118 patients awaiting cardiac transplantation were found to be sensitized. These patients underwent plasmapheresis followed by 20 gm of intravenous immunoglobulin G (IVIG) immediately prior to cardiac transplantation. Group 1 was compared to the remaining 102 patients with a PRA <10% (Group 2). RESULTS: Despite more patients in Group 1 having a positive crossmatch, pulmonary hypertension, and requiring mechanical circulatory support, there was no statistically significant difference in length of stay or mortality at a mean follow-up of 21.6+/-15.0 months. There was no difference in the occurrence of mild, moderate or severe cellular rejection or humoral rejection in these sensitized patients when compared to Group 2. CONCLUSIONS: Pretransplant plasmapheresis followed by intravenous immunoglobulin G may be an effective therapy that obviates the need for a prospective crossmatch and allows sensitized patients to undergo cardiac transplantation. There is no increase in the post transplant length of stay, occurrence of rejection or short term mortality. Long term follow up is necessary to evaluate whether there is a difference in the development of late rejection, transplant vasculopathy and survival.

Effective oral ganciclovir prophylaxis against cytomegalovirus disease in heart transplant recipients.

The presented data show the combined sequential use of i.v. G for 14 days followed by PO G for 90 days is a much more effective prophylaxis for CMVD after heart transplantation than use of i.v. G for 14 days followed by PO A for 90 days. A need for hospitalization due to CMVD is significantly reduced by this new strategy. The follow-up in group II is shorter than in group I but is now at least 6 months in group II, without any new cases in the first 6 months after cardiac transplantation. Some currently unknown adverse effect of prolonged PO G, which may be present, is not identified in this analysis.

Influence of preoperative transpulmonary gradient on late mortality after orthotopic heart transplantation.

We reviewed the transpulmonary gradient, pulmonary arterial systolic pressure, pulmonary vascular resistance (Wood units), and pulmonary vascular resistance index (Wood units X Body surface area), recorded preoperatively in 109 recipients aged 44.6 +/- 13.5 (mean +/- SD) years who underwent orthotopic heart transplantation between March 1984 and March 1988, to identify which measure of pulmonary hypertension most accurately predicts poor outcome after orthotopic heart transplantation. These recipients were followed up as many as 57 (24.7 +/- 14.5) months after their transplant procedure. Preoperative hemodynamic values were as follows: transpulmonary gradient, 10.4 +/- 4.7 mm Hg; pulmonary artery systolic pressure, 53.6 +/- 14.8 mm Hg; pulmonary vascular resistance, 2.7 +/- 1.8 Wood units; pulmonary vascular resistance index, 4.9 +/- 2.7. Nineteen recipients died within 1 year after orthotopic heart transplantation. Causes of death were acute rejection (8), chronic rejection (1), infection (2), nonspecific orthotopic heart transplant failure (4), bowel ischemia (1), pancreatitis (1), lymphoma (1), and liver failure (1). Preoperative pulmonary arterial systolic pressure, pulmonary vascular resistance, and pulmonary vascular resistance index were not predictive of 1-month, 6-month, or 1-year mortality. One-month mortality rates of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg and of those with transpulmonary gradient less than 12 mm Hg were not significantly different (11% vs 3%; p = 0.12). The 6-month mortality rate of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg, however, was five times greater than that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (24% vs 5%; p = 0.003), and 12-month mortality of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg was increased sevenfold when compared with that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (36% vs 5%; p = 0.0005). These results suggest that presently used measures of pulmonary hypertension do not predict mortality in the first month after orthotopic heart transplantation, but that elevated preoperative transpulmonary gradient is associated with a significant increase in mortality at 6 and 12 months after orthotopic heart transplantation. Prospective randomized trials are needed to determined whether extended preload and afterload reduction before and/or after transplant will favorably influence long-term prognosis of orthotopic heart transplant recipients with elevated preoperative transpulmonary gradient.

Use of cyclosporine in the mouse heterotopic heart transplant model.

We refined the mouse ear-heart transplant model developed by Fulmer and coworkers and tested cyclosporine as a sole immunosuppressive agent in this model. Three-week-old CBA mice were used as heart recipients, and unsexed newborn BALB/c mice were used as heart donors. The heart grafts were examined for visible pulsations at 10-fold to 20-fold magnification daily for the first 10 days and every other day thereafter. Graft electrocardiograms were also obtained on the same schedule. Preliminary studies had established that a dose of 15 mg/kg/day was the optimal cyclosporine dose in our model. This dose was administered subcutaneously to each of two treatment groups. Group 2 received this dose for the entire 30-day experimental period. Group 3 received this dose for the first 16 days of the experimental period. Group 1 consisted of allografts receiving no immunosuppression. Group 1 grafts showed evidence of initial successful engraftment by day 7; however, by day 13 none of the grafts remained viable. In group 2, 19 of 23 grafts remained viable for the entire experimental period. In group 3, all of the grafts remained viable until day 17 (after day 16 cyclosporine was discontinued) and rapidly lost evidence of viability thereafter. By day 21, none of the grafts in group 3 remained viable. Survival curves for the three groups as determined by electrocardiogram and visible pulsations were constructed, and the differences between the curves were significant (p = 0.001). The results of this study demonstrate the potential usefulness of the ear-heart transplantation model in screening immunosuppressive agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of power spectral analysis of respiratory sinus arrhythmia to detect graft rejection.

Some evidence has suggested that graft rejection in heart transplant recipients is accompanied by sinus node dysfunction. To test this hypothesis the electrocardiograms of 21 orthotopic heart transplant recipients receiving cyclosporine were recorded at regularly scheduled biopsies. This resulted in 105 good quality recordings of at least 10 minutes each. All exhibited normal sinus rhythm. These recordings were then processed through patented digital routines that calculated the power spectrum of the RR intervals. All recordings exhibited Mayer wave and respiratory sinus arrhythmia (RSA) periodicities. Peak spectral power of RSA (PSP-RSA) demonstrated good repeatability at 2 weeks (r = 0.81). A paired t test comparing the baseline PSP-RSA in eight subjects who experienced rejection episodes with their individual average PSP-RSA during periods of rejection revealed a significant decrease (p = 0.039). As a global measure, PSP-RSA greater than 1 (natural logarithmic scales) demonstrated a sensitivity of 1.0, specificity of 0.42, positive predictive value of 0.22, and negative predictive value of 1.0. These tentative results demonstrate that PSP-RSA may be a sensitive, noninvasive marker for graft rejection of heart transplant patients receiving cyclosporine for immunosuppression. A larger, more extensive study needs to be conducted to confirm these results.

Combined therapy with dobutamine and amrinone in severe heart failure. Improved hemodynamics and increased activation of the renin-angiotensin system with combined intravenous therapy.

The hemodynamic and hormonal responses to dobutamine alone and with the addition of amrinone were studied in ten patients with severe heart failure. Dobutamine significantly increased heart rate, cardiac index, and stroke volume index and significantly decreased mean right atrial and systemic arterial pressures and systemic and pulmonary vascular resistance. The addition of amrinone further decreased significantly mean right atrial, pulmonary arterial, and pulmonary arterial wedge pressures and systemic vascular resistance, while heart rate rose. The response of the cardiac index was variable, increasing in seven and decreasing in three patients. Plasma renin activity rose significantly with dobutamine and further increased with amrinone. We conclude that in most patients with severe heart failure, amrinone, when combined with dobutamine, improves hemodynamics. The further increase in heart rate, variable effects on the cardiac index, and marked activation of the renin-angiotensin system suggest caution and potential limitations in the use of this combination.

The effect of heart transplantation on Cheyne-Stokes respiration associated with congestive heart failure.

Cheyne-Stokes respiration occasionally accompanies the terminal stages of congestive heart failure. We describe this association in a patient requiring heart transplantation. The gradual abatement of Cheyne-Stokes respiration after transplantation supports the delayed circulatory time theory as the mechanism for Cheyne-Stokes respiration in these patients.

Effects of indomethacin on coronary hemodynamics, myocardial metabolism and anginal threshold in coronary artery disease.

The effects of orally administered indomethacin or placebo on coronary hemodynamics were studied in 23 patients with coronary artery disease. After indomethacin administration the systemic arterial pressure increased by 12 +/- 4% and the myocardial oxygen consumption by 24 +/- 11%. Coronary sinus flow did not change and coronary vascular resistance increased slightly. Oxygen saturation of the arterial blood did not change, but coronary sinus saturation decreased substantially. Hemodynamic values returned to normal 150 minutes after administration of indomethacin. During rapid atrial pacing, coronary sinus flow increased 79 +/- 14% above the rest value when pacing was done before indomethacin administration; only a 56 +/- 12% increase was seen when pacing was repeated after indomethacin. Peak heart rate achieved during atrial pacing, severity of angina and the degree of ST-segment depression were not altered by indomethacin treatment. Orally administered indomethacin has a mild coronary vasoconstrictive effect that does not interfere substantially with the expected increase in myocardial blood flow during rapid atrial pacing. Anginal threshold is not altered by orally administered indomethacin.

Ischemic injury to the brachial plexus following subclavian flap aortoplasty.

An ischemic brachial plexus lesion developed 6 days postoperatively in an infant undergoing subclavian flap aortoplasty for coarctation. To our knowledge, this complication has never been previously reported. Types of postoperative brachial plexus lesions are discussed. The blood supply to the brachial plexus is described. An ischemic lesion of the plexus should be suspected when brachial palsy follows operations that involve sacrifice of the subclavian artery.

The modified blalock-taussig shunt using microporous expanded polytetrafluoroethylene (PTFE).

From May 1977 to February 1981, 36 modified Blalock-Taussig shunts were performed in 34 patients for a variety of cyanotic congenital cardiac lesions. Microporous expanded PTFE was utilised as a conduit between the subclavian artery and the ipsilateral pulmonary artery. Graft diameter was 4 mm in 15 cases, 6 mm in 17 cases, and 8 mm in the remaining 4. Age at time of operation ranged from one day to 22 years. Fourteen shunts were performed in infants less than one year old. Overall operative mortality was 5.5 per cent. There were 6 shunt failures (16.6%) and all were the smallest diameter graft. Overall actuarial shunt survival at 2 years was 81.2 per cent. This shunt has all the advantages of the original Blalock-Taussig procedure. In addition, it preserves the integrity of the subclavian artery and minimizes the technical problems associated with the classical shunt. It is the procedure of choice at our hospital.