Szabolcs Szentpetery

Arterial baroreflex abnormalities in heart failure. Reversal after orthotopic cardiac transplantation.

Arterial baroreflex control of the heart and peripheral circulation is markedly impaired in humans and animals with congestive heart failure. After reversal of heart failure in animal models, arterial baroreflex control of heart rate remains impaired for up to 8 months. Cardiac transplantation restores normal ventricular function and completely reverses heart failure, but does it normalize arterial baroreflex control of heart rate in humans? We studied baroreflex sensitivity in 11 patients with severe heart failure, six normal control patients, and 23 patients at 2 weeks to 4 years after orthotopic cardiac transplantation. Baroreflex sensitivity was assessed with intravenous bolus injections of phenylephrine and is expressed as change in RR or PP interval (msec) per millimeters of mercury rise in systolic arterial pressure. Atrial rate of both donor (denervated) and recipient (innervated) atria were measured in the transplant group. Baroreflex sensitivity in patients with severe heart failure was 2.0 +/- 0.3 msec/mm Hg, but in patients after cardiac transplantation, it was 13.0 +/- 0.9 msec/mm Hg (p less than 0.001). The responses in the transplant group were similar to those observed in normal controls (10 +/- 1.2 msec/mm Hg, p = NS). Our data indicate that patients with severe congestive heart failure have marked abnormalities of baroreflex control, which are reversed as early as 2 weeks after cardiac transplantation. In view of this rapid reversal, we consider it unlikely that abnormal baroreflex sensitivity seen in heart failure is due to structural alterations in the baroreceptors. We speculate that neurohumoral rather than structural abnormalities account for depressed baroreflex sensitivity in heart failure.

Surgical management of heparin-associated thrombocytopenia: Strategies in the treatment of venous and arterial thromboembolism

We report the vascular surgical strategies and results in 13 patients with heparin-associated thrombocytopenia and describe useful in vitro techniques for the evaluation of anticoagulant therapy. Thirteen of 40 patients with heparin-associated thrombocytopenia had 18 cardiovascular procedures done to save life or limb. Greenfield filters were placed in eight patients to prevent pulmonary embolism. Eight patients had 10 arterial procedures, with alternative anticoagulation that used dextran or warfarin in five cases. In three cases iloprost, a derivative of prostacyclin and a potent platelet inhibitor, was infused intraoperatively and heparin was given. Both the use of alternative anticoagulants and platelet suppression by iloprost were clinically effective strategies. The concurrent measurement of plasma levels of beta-thromboglobulin and fibrinopeptide A in two patients confirmed that both approaches can successfully prevent activation of platelets and plasma coagulation during arterial surgery. One operative death occurred; all vascular reconstructions remained patent at 3 to 6 months. In two patients who received heparin alone for arterial surgery, both procedures resulted in thrombosis and limb loss. When major venous thromboembolism is complicated by heparin-associated thrombocytopenia, insertion of a Greenfield vena cava filter should be considered if there is significant risk of pulmonary embolism. When necessary, arterial surgery is feasible in patients with heparin-associated thrombocytopenia if alternative anticoagulation or adequate suppression of platelet reactivity can be achieved.

Long-distance transportation of human hearts for transplantation.

Abstract This communication describes the preservation and long-distance (203 to 1,400 km) transportation of 6 human donor hearts with a hemodynamically successful short-term outcome in the recipients, all of whom were critically ill from end-stage cardiac failure. These techniques of long-distance donor heart transportation, not previously described in the human, offer prospects for markedly improving the logistics of heart transplantation in critically ill recipients who require immediate transplantation in face of limited local capability for securing an adequate donor heart. These systems may also prove of value in cardiac transplant protocols, such as rapid retransplantation during rejection and programmed protocols for recipient pre-treatment to promote enhancement of graft survival, that require obtaining a donor heart in an expedient manner.

Cyclosporine in Cardiac Transplantation

Cyclosporine is a new immunosuppressive drug that acts early in the exposure of a host to allogeneic stimulation. It is a peptide of fungal origin. It has selective action on T cells, leaving the other cells of the immune system intact. It acts by preventing the function of the early activation signals of T cells, such as the acquisition of receptors for Il 2 and Il 1. It is lipophilic, moderately well absorbed by the gut, and metabolized by the liver. Factors affecting absorption or hepatic metabolism alter the amount of cyclosporine available in the circulation. Circulating levels can be measured by radioimmunoassay or HPLC. Doses should be tailored to trough levels taken approximately 12 hours after an oral or intravenous dose or to individual pharmacokinetic curves. The drug is nephrotoxic, hepatotoxic, and neurotoxic. In addition, cyclosporine has been associated with hypertension, hemolytic-uremic syndrome, increased incidence of intravascular thrombotic events, hypertrichosis, gum hyperplasia, pericardial effusion, and lymphoproliferative disorders. Despite these complications, cyclosporine usage seems to have improved short-term cardiac allograft survival and to have reduced the complications associated with side effects of steroids. As a result, cyclosporine has spawned a resurgence of interest in cardiac transplantation, which will be of great benefit in prolonging the lives of patients with end-stage cardiac disease.

Subnormal heart period variability in heart failure: effect of cardiac transplantation.

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.

Pull-through esophagectomy without thoracotomy for esophageal carcinoma.

Seventeen consecutive patients underwent pull-through esophagectomy using blunt dissection from laparotomy and cervical incisions for carcinoma of the esophagus. Fifteen patients had a middle-third lesion while 2 patients had a distal-third lesion. The gastrointestinal tract was reconstructed using primary gastroesophagostomy in 15 patients and colon interposition in 2. Both the colon and stomach were placed through the posterior mediastinum. The surgical technique and results are described in detail. There were two major complications. One patient died of massive gastric hemorrhage on the eighth postoperative day in spite of emergency operation. Another patient sustained a tear of the membranous trachea at the time of blunt dissection. This was repaired through a right thoracotomy without difficulty. Esophagectomy using blunt dissection offered excellent palliation and resulted in little morbidity in our series. The shortened operating time, minimal blood loss, total lack of postoperative chest pain, minimal pulmonary complications, and the benefit of a cervical anastomosis are several advantages compared with the present surgical approaches.

Pretransplant transfusions in cardiac allograft recipients.

The role of pretransplant transfusion in cardiac allograft recipients was determined retrospectively in 68 patients. Three groups were studied: group 1 (n=29) received no pretransplant transfusion, group 2 (n=15) received transfusion over one year prior to transplantation, and Group 3 (n=24) received 5 or 10 50–100 ml units of random donor red blood cells or buffy coat 2–4 weeks prior to transplantation. Data were analyzed for survival, number of rejection episodes, and number of infections. Immunosuppression included azathioprine, prednisone, and antithymocyte globulin. Survival in transfused patients (groups 2 and 3) was 68% and 51% at 1 and 5 years, respectively, while in the nontrans-fused population (group 1) it was 35% and 16%. The incidence of rejection episodes per year of survival was similar in the three groups (group 1: 1.3, group 2: 1.1, group 3: 1.3; P<0.05). The number of infections per year of survival were greater in the transfused patients but this did not achieve statistical significance (group 1: 1.0, group 2: 1.2, group 3: 1.7; P<0.05). Thus, we conclude that cardiac transplant recipients who have received blood transfusions prior to transplantation may have enhanced survival over patients who have not received preoperative transfusions.

Symptomatic abdominal aortic aneurysms in long-term survivors of cardiac transplantation

Herein we report the only two long-term survivors of cardiac transplantation who underwent successful repair of symptomatic abdominal aortic aneurysms since the advent of cyclosporine therapy in 1983. Review of the worlds literature indicates that the only two recorded cases of repair of symptomatic abdominal aortic aneurysms after cardiac transplantation occurred before the use of cyclosporine. The presentation and clinical course of our patients recently treated are presented, and perioperative care and immunosuppressive management are outlined. As the number of long-term survivors after cardiac transplantation increases, the incidence of other atherosclerotic complications including abdominal aortic aneurysm is likely to become more common, requiring extended cardiovascular follow-up.

Changing concepts in the treatment of penetrating cardiac injuries.

Thirty consecutive patients with penetrating wounds to the heart underwent surgery at the Medical College of Virginia Hospital. Classical signs of tamponade usually were not present. A precordial wound, positive pericardiocentesis, and shock were the most common indications of cardiac injury. Immediate operation is recommended for all penetrating injuries; pericardiocentesis is employed only for a diagnostic tool and for emergency relief of tamponade.

Endocarditis due to accidental penetrating foreign bodies

A 15 year old boy had an eight month history of recurrent fever, malaise and poor appetite. Chest roentgenogram revealed a foreign object overlying the right ventricle. Multiple blood cultures grew Enterobacter cloacae. The patients condition improved and blood cultures became negative following gentamicin and carbenicillin therapy. E. cloacae was isolated from the foreign body (a finishing nail) at surgery. Antimicrobial therapy was continued for a total of 30 days, and the patient made an uneventful recovery.