Cardioembolic stroke: diagnosis and treatment.

Cerebrovascular disease is a major cause of morbidity and mortality. Approximately 75% to 80% of strokes and transient ischemic attacks are due to vascular disease within the cartoid or cerebral circulation. Of the remaining 20% to 25%, perhaps 50% are due to a cardioembolic event. Transesophageal echocardiography is the best screening test available for an unexplained cerebrovascular event. Anticoagulation with warfarin is indicated in the majority of cases of cardioembolic emboli. Atrial fibrillation is a major risk factor for stroke and prophylactic anticoagulation is warranted.

Cardiac transplantation: role of endomyocardial biopsy and immunosuppressive agents.

The field of cardiac transplantation has made tremendous strides since the first transplant procedure in 1967. This paper reviews the role of endomyocardial biopsy to diagnose and follow rejection as well as the standard immunosuppressive regimens employed. With continued refinements in immunosuppressive therapy, further improvements in mortality and morbidity rates should be realized.

Cardiac transplantation: an overview of recipient selection.

Cardiac transplantation is an accepted treatment for end-stage heart disease. Potential recipients are carefully screened in order to best place the short supply of donor organs with the best recipient. The success of heart transplantation in the United States today is directly related to careful donor and recipient selection criteria and improvements in immunosuppression.

Vagal responses to adjustable sutures in strabismus correction.

The oculocardiac reflex is a recognized complication of ocular stimulation, precipitated most commonly by traction on the extraocular muscles. To determine the true incidence of occurrence of the oculocardiac reflex during suture adjustments, 20 patients undergoing suture adjustment were monitored for blood pressure, heart rate, and rhythm abnormalities during the suture adjustment. A control group of ten patients with strabismus were studied postoperatively for comparison. Thirteen study patients and two control patients were noted to have a vagal response (P less than .001). The most common response noted was a decrease in heart rate in 15 patients. Only two patients were symptomatic during vagal response (one patient became light-headed and another had an episode of nausea and vomiting). Suture adjustment was found to be the most common triggering event in precipitating vagal responses. Surgeons performing suture adjustment in strabismus correction should be cognizant of vagal responses so that they may properly inform patients of this possibility and take steps to minimize its occurrence.

Beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin.

An increase in cardiac beta-adrenergic sensitivity or beta-receptor density or both has been described in several animal species after denervating the heart. The transplanted human heart is also denervated and, therefore, may exhibit supersensitivity to beta-adrenergic agonists and an increase in beta-adrenergic receptor density. In 16 patients examined 1-3 months after orthotopic cardiac transplantation, beta-adrenergic receptor density measured by [125I]iodocyanopindolol binding in endomyocardial biopsy specimens was not significantly different in transplant recipients compared with normal controls (transplant = 1,429 +/- 199, control = 1,728 +/- 263 fmol/g wet wt; p = NS). However, when normalized to Lowry protein, the [125I]iodocyanopindolol in beta-adrenergic receptor density in biopsy tissue from transplant recipients was significantly lower than in tissue from controls (transplant = 58.1 +/- 6.2, control = 93.5 +/- 13.4 fmol/g Lowry protein; p = 0.011). Atrial sinus node activity of the denervated donor heart and the innervated atrial cuff of the native recipient heart could be detected on the surface electrocardiogram in six patients. In these six patients, the heart rate response to graded infusions of epinephrine (taken up by the adrenergic nerve terminals) and isoproterenol (not taken up by the adrenergic nerve terminals) was measured. The epinephrine dose-response curve in transplanted donor atria was significantly to the left of the native recipient atrial dose-response curve (p less than 0.0001). The isoproterenol dose-response curves for native and transplanted atria were not different. We conclude that myocardial beta-adrenergic receptors are not increased in human orthotopic cardiac allografts and that there is no evidence for beta-receptor-mediated supersensitivity of postsynaptic origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunosuppressive efficacy of vincristine in heart transplantation: a preliminary report.

Because vincristine has immunosuppressive activity in animal models, has specific cytotoxic effects on lymphocytes, and does not have overlapping toxicity with other immunosuppressive agents, we designed a prospective randomized trial to evaluate the efficacy of the addition of vincristine to standard immunosuppressive therapy in heart transplantation. Patients received equine antithymocyte globulin for the first week or murine antihuman mature T cell (OKT3) monoclonal antibody for the first 2 weeks after transplantation and were maintained on azathioprine and cyclosporine. A steroid pulse was administered 1 day after completion of antithymocyte globulin or OKT3 monoclonal antibody and tapered off over 21 days. Vincristine was given at 0.025 mg/kg intravenously for eight dosages over 12 weeks, beginning 2 days after completion of antithymocyte globulin or OKT3 monoclonal antibody. Fifty-two patients were randomized (26 were given vincristine, and 26 were not). The addition of vincristine to the regimen of patients receiving antithymocyte globulin resulted in significantly fewer episodes of rejection at 1 month (vincristine, 0.2 +/- 0.1; no vincristine, 1.2 +/- 0.2; p less than 0.001), at 3 months (vincristine, 1.2 +/- 0.1; no vincristine, 2.5 +/- 0.3; p less than 0.001), and at 6 months (vincristine, 1.9 +/- 0.2; no vincristine, 2.9 +/- 0.3; p less than 0.001). It also resulted in significantly more patients being successfully weaned off daily steroids (vincristine, 67%; no vincristine, 20%; p = 0.04). The addition of vincristine to the regimen of patients receiving early rejection prophylaxis with OKT3 monoclonal antibody did not alter rejection incidence or steroid usage.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody.

OKT3 monoclonal antibody is a murine monoclonal antibody specific for the T lymphocyte T3 cell surface receptor that mediates antigen recognition. The use of OKT3 monoclonal antibody for the treatment of cardiac allograft rejection refractory to conventional therapy with high-dose steroids and antithymocyte globulin is described. Seven patients received 5 mg of OKT3 monoclonal antibody intravenously per day for 10 to 14 days. Diagnosis of moderate or severe rejection was made in all seven from right ventricular endomyocardial biopsy. Biopsy was repeated 48 to 72 hours and seven to 10 days after OKT3 monoclonal antibody was begun. With treatment, four patients had a complete response, with improvement on both early and late biopsy. Two patients had partial responses, with improvement on early biopsy followed by worsening rejection on late biopsy. One patient died of graft failure six hours after receiving OKT3 monoclonal antibody. Adverse events were common in the first two days of therapy but were well tolerated. It is concluded that OKT3 monoclonal antibody is useful in the treatment of refractory cardiac allograft rejection.