Arun K. Singhal

Management of the sensitized cardiac recipient : the use of plasmapheresis and intravenous immunoglobulin

Abstract:  Previously, we reported that the combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg) allow sensitized patients to undergo orthotopic heart transplantation (OHT), even across a positive crossmatch. In the current study, the effect of that combination, PP +IVIg, on survival of a larger group of such recipients is investigated. The latter group (I) consisted of 35 sensitized patients who received PP + IVIG together with standard immunosuppressive drugs. Rejection was seen in 11 patients, findings strongly suggestive of a vascular (humoral) being identified in five of those cases. Four deaths occurred, two of them in the immediate post‐operative period, one after almost six months, and one after almost two yr post‐OHT. Follow‐up range 4.5 months to 7.8 yr post‐OHT (average = 1.1 yr). Patient survival was analyzed after generation of a Kaplan–Meier plot. Comparison with a control OHT group (II) given standard immunosuppressive drugs only (N = 276) showed enhanced survival of group I (p = 0.0414 by log‐rank test). We conclude that the combination of PP and IVIG (i) is associated with declines in T‐ and B‐percent‐reactive antibody and in crossmatch positivity, and (ii) is very useful in the management of the sensitized cardiac patient undergoing OHT, often allowing a successful outcome to transplantation in the face of a positive crossmatch.

Intralobar sequestration in the middle-aged and elderly adult: recognition and radiographic evaluation

Intralobar sequestration is a rare cause of recurrent bronchitis, pneumonia, or hemoptysis that is often misdiagnosed both because of a lack of recognition of radiologic findings and a low expectation of the disease, particularly in middle-aged and elderly adults. Definitive therapy is surgical, and preoperative delineation of anatomy is essential. We present 2 cases from our institution that were atypical in presentation and used different radiographic imaging modalities. A review of the literature pertaining to presentations in older adults and radiographic delineation of these lesions follows.

Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia–reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts

BACKGROUND Hearts from non-heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals. METHODS Hearts from Yorkshire pigs (100 kg) were studied in 3 groups. Group 1 (control) hearts were surgically removed while beating. Group 2 hearts were harvested from animals made hypoxic by discontinuing mechanical ventilation for 30 minutes. Group 3 hearts were hypoxic as in Group 2, but these animals received adenosine (40 mg) and cariporide (400 mg) 10 minutes before stopping ventilation. Cardiac function in all groups was assessed ex vivo in a working heart apparatus in which pressure and flow measurements were made over 3 hours. Controlled reperfusion in Group 3 hearts used leukocyte-depleted blood perfusate containing free radical scavengers. Myocardial injury was assessed on the basis of perfusate creatine phosphokinase activity and histopathologically determined injury score. RESULTS Groups 1 and 3 hearts could be resuscitated to perform work equivalently during the entire reperfusion period and showed positive responses to increases in pre-load and norepinephrine. Group 2 hearts could not perform work. After 3 hours, Group 2 hearts showed significantly higher creatine phosphokinase and histopathologic injury scores compared to with Groups 1 and 3, which were not significantly different from each other. CONCLUSIONS Pharmacologic pre-conditioning and controlled reperfusion effectively protect non-beating porcine hearts from injury after 30 minutes of hypoxia/ischemia in situ.

Off-pump technique for insertion of a HeartMate vented electric left ventricular assist device

The number of patients awaiting heart transplantation has increased exponentially during the past 10 years, while the number of donor organs has remained unchanged . Alternatives to cardiac transplantation, such as left ventricular assist devices (LVADs), have been shown to decrease mortality and increase the quality of life in patients with end-stage heart failure . It has recently been proposed that these devices may become a destination therapy for patients with end-stage heart failure and thus allow definitive treatment for those who otherwise may not be able to receive or qualify for heart transplantation . Cardiopulmonary bypass (CPB) is routinely required for implantation of LVADs. However, the well-described complications of CPB may exacerbate multiple organ failure and increase blood product transfusions during and after the operation. Recent technologic advances, including cardiac stabilization devices, have allowed coronary artery bypass surgery to be performed without CPB. We present a technique for insertion without cardiopulmonary bypass of a HeartMate Vented Electric LVAD (Thoratec Corporation, Pleasanton, Calif).

Off-pump technique for Thoratec left ventricular assist device insertion

We present a case of left ventricular assist device (Thoratec; Thoratec Laboratories Corp, Pleasanton, CA) insertion performed through a left thoracotomy without cardiopulmonary bypass in a patient with severe end-stage congestive heart failure with renal and respiratory dysfunction and a history of multiple cardiac operations.

HUMAN MYOCARDIAL CELL LINES GENERATED WITH SV40 TEMPERATURE-SENSITIVE MUTANT TSA58

SummaryConditionally transformed human myocardial cell lines would be a valuable resource for studying human cardiac cell biology. We generated clonal human fetal cardiocyte cell lines by transfection of fetal ventricular cardiac cell clones with a plasmid containing a replication-defective mutant of the temperature-sensitive SV40 strain tsA58. Multiple resulting cell lines showed similar features, namely: (1) T antigen (TAg) expression at both permissive (34°C) and restrictive (40.5°C) temperatures; (2) extended growth capacity in comparison with parental wild type, when grown at the permissive temperature; (3) both temperature-dependent and serum-responsive growth, and; (4) an incompletely differentiated fetal phenotype which was similar at both permissive and restrictive temperatures and in the presence and absence of serum. The transformed myocyte phenotype was demonstrated using immunocytochemistry, Western and Northern blotting, and reverse transcription-polymerase chain reaction (RT-PCR). Cell lines expressed skeletal α-actin, atrial natriuretic peptide (ANP), and keratins, but no sarcomeric myosin heavy chain or desmin. Immunoreactive sarcomeric actin was expressed predominantly as a truncated protein of approximately 38 kD. The phenotype of the transformed cells differs from that of the wild-type parental cells as well as from those reported by others who have used TAg to immortalize rodent or human ventricular myocytes. Our cell lines should provide a useful tool for study of the molecular mechanisms regulating growth and differentiation in human cardiac muscle cells.

Successful treatment of esophageal cancer with transhiatal esophagectomy after heart transplantation

A 55-year-old heart transplant recipient with reflux esophagitis presented for routine endoscopic surveillance of an area of Barretts metaplasia initially seen 3 years previously. Esophagogastroduodenoscopy revealed adenocarcinoma at 33 cm from the incisors. The preoperative clinical stage was T1N0M0 by endoscopic ultrasound. Transhiatal esophagectomy was performed with R0 resection of the cancer, and the patient recovered uneventfully. Pathologic examination confirmed esophageal adenocarcinoma (T1N0M0) in Barretts mucosa. The patient is doing well, and has no evidence of disease after 18 months.