Normothermic ex vivo perfusion provides superior organ preservation and enables viability assessment of hearts from DCD donors.

The shortage of donors in cardiac transplantation may be alleviated by the use of allografts from donation after circulatory death (DCD) donors. We have previously shown that hearts exposed to 30 min warm ischemic time and then flushed with Celsior supplemented with agents that activate ischemic postconditioning pathways, show complete recovery on a blood-perfused ex vivo working heart apparatus. In this study, these findings were assessed in a porcine orthotopic heart transplant model. DCD hearts were preserved with either normothermic ex vivo perfusion (NEVP) using a clinically approved device, or with standard cold storage (CS) for 4 h. Orthotopic transplantation into recipient animals was subsequently undertaken. Five of six hearts preserved with NEVP demonstrated favorable lactate profiles during NEVP and all five could be weaned off cardiopulmonary bypass posttransplant, compared with 0 of 3 hearts preserved with CS (p < 0.05, Fisher's exact test). In conclusion, DCD hearts flushed with supplemented Celsior solution and preserved with NEVP display viability before and after transplantation. Viability studies of human DCD hearts using NEVP are warranted.

Methotrexate in the Treatment of Recalcitrant Nodular Vasculitis.

We report a case of recalcitrant nodular vasculitis in a 23 years old male who was treated successfully with methotrexate. He presented to our Dermatology out Patient Department, Tribhuvan university teaching hospital with complaints of recurrent painful discharging ulcer over bilateral calf and lower legs of three years duration. The diagnosis of nodular vasculitis was made on the basis of the clinical presentation and the histopathological findings. The patient was treated with anti-tuberculosis treatment with initial good response; however the lesions persisted later on, despite completing the course of ATT. The patient did not respond to treatment with systemic corticosteroids also. On starting methotrexate, the lesion started healing within a period of two weeks and there was significant improvement in subsequent one month. This case report highlights the efficacy of methotrexate in the treatment of recalcitrant nodular vasculitis.

Increasing the tolerance of DCD hearts to warm ischemia by pharmacological postconditioning.

Donation after circulatory death (DCD) offers a potential additional source of cardiac allografts. We used a porcine asphyxia model to evaluate viability of DCD hearts subjected to warm ischemic times (WIT) of 20­40 min prior to flushing with Celsior (C) solution. We then assessed potential benefits of supplementing C with erythropoietin, glyceryl trinitrate and zoniporide (Cs), a combination that we have shown previously to activate ischemic postconditioning pathways. Hearts flushed with C/Cs were assessed for functional, biochemical and metabolic recovery on an ex vivo working heart apparatus. Hearts exposed to 20-min WIT showed full recovery of functional and metabolic profiles compared with control hearts (no WIT). Hearts subjected to 30- or 40-min WIT prior to C solution showed partial and no recovery, respectively. Hearts exposed to 30-min WIT and Cs solution displayed complete recovery, while hearts exposed to 40-min WIT and Cs solution demonstrated partial recovery. We conclude that DCD hearts flushed with C solution demonstrate complete recovery up to 20-min WIT after which there is rapid loss of viability. Cs extends the limit of WIT tolerability to 30 min. DCD hearts with ≤30-min WIT may be suitable for transplantation and warrant assessment in a transplant model.

Enhanced preservation of pig cardiac allografts by combining erythropoietin with glyceryl trinitrate and zoniporide.

Erythropoietin has a tissue-protective effect independent of its erythropoietic effect that may be enhanced by combining it with the nitric oxide donor glyceryl trinitrate (GTN) and the sodium-hydrogen exchange inhibitor zoniporide in rat hearts stored with an extracellular-based preservation solution (EBPS). We thus sought to test this combination of agents in a porcine model of orthotopic heart transplantation incorporating donor brain death and total ischaemic time of approximately 260 min. Pig hearts were stored in one of four storage solutions: unmodified EBPS (CON), EBPS supplemented with GTN and zoniporide (GZ), EBPS supplemented with erythropoietin and zoniporide (EZ), or EBPS supplemented with all three agents (EGZ). A total of 4/5 EGZ hearts were successfully weaned from cardiopulmonary bypass compared with only 2/5 GZ hearts, 0/5 CON hearts and 0/5 EG hearts (p = 0.017). Following weaning from bypass EGZ hearts demonstrated superior contractility and haemodynamics than GZ hearts. All weaned hearts displayed impaired diastolic function. Release of troponin I from EGZ hearts was lower than all other groups. In conclusion, supplementation of EBPS with erythropoietin, glyceryl trinitrate and zoniporide provided superior donor heart preservation than all other strategies tested.

Clinical profile of patients with pleural effusion admitted to KMCTH.

BACKGROUND: Pleural effusion is the common findings in patients presenting with cardiopulmonary symptoms but specific studies are lacking in Nepal. OBJECTIVE: The main objective of this study is to fi nd out the various causes of pleural effusion, their mode of clinical presentation and laboratory analysis of blood and pleural fluid to aid diagnosis of patients with pleural effusion. MATERIALS AND METHODS: Retrospective data from July 2009 to July 2007 from all the cases diagnosed with pleural effusion were taken. Altogether 100 cases diagnosed with pleural effusion by chest X-ray (Posterior- Anterior and Lateral view) and Ultrasonogram of the chest were studied. The following parameters were analysed: Patients demographic profile, causes, location (Unilateral, Bilateral), Blood haemoglobin and count, sputum profile, Monteux test, chest X-ray and USG findings and pleural fluid analysis[Biochemical, Haematological, Microbiological (culture and stain) and cytological]. This study was analysed by using SPSS 16. RESULTS: The mean age of the patient was 44.89 +/- 21.59 and must patients with pleural effusion belong to age group 21-30. Most common cause of pleural effusion was found to be tubercular effusion followed by parapneumonic effusion. Right sided effusion was seen in most cases of tubercular parapneumonic and malignant effusion whereas bilateral effusion was seen in 87.5% of the patient (7 out of 8) having congestive heart failure and all cases of renal disease (4 out of 4). Shortness of breath (83%), cough (67%) and fever (66%) are the most common mode of clinical presentation. CONCLUSION: Our study concluded that the most common cause of unilateral pleural effusion is tuberculosis followed by parapneumonic effusion and most cases of those belong to younger age group (21-30 yrs) and most common cause of bilateral pleural effusion is congestive cardiac failure.

Midterm results of the Ross procedure.

OBJECTIVE: The lack of durable bioprosthetic valves and the inherent risks associated with anticoagulation for mechanical valves have led to the continued use of the Ross procedure, particularly in the pediatric population. METHODS: We have reviewed our mid-term results retrospectively, following the Ross operation in both pediatric and adult groups. RESULTS: Over a 11-year period from August 1991 to August 2002, 60 patients underwent the Ross procedure. The median age was 15 years (6-804 months), of which 63% were males and 55% were under the age of 20 years. The main indications were: aortic stenosis in 47 patients; aortic insufficiency in 6 patients; and mixed aortic valve disease in 28 patients. Fifteen patients had previously undergone balloon dilatation of the aortic valve, 4 had open valvotomy and 3 had both valvuloplasty procedures. The pulmonary autograft was implanted as a sub-coronary implant until 1995 (30%) after which time it was implanted using a partial inclusion cylinder technique (70%). There have been no deaths reported in this series. Over a median follow-up period of 59 months (2-122 months), there have been four re-operations for repair of autograft leak, and 2 adult patients have had autograft replacements. CONCLUSIONS: Despite the increased technical complexity, the Ross procedure can be performed safely in both paediatric and adult populations with satisfactory medium term results.

Gerbode's defect resulting from infective endocarditis.

We present a report of a Gerbode's defect (left ventricular-right atrial communication) resulting from bacterial endocarditis in a 63-year-old man. Also presented is a brief overview of the literature and a possible preoperative echocardiographic diagnostic criterion relating to this unusual condition.

[(18)F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer.

OBJECTIVE: Positron emission tomography (PET) is being increasingly used as an accurate and non-invasive modality in diagnosis, staging and post-therapy assessment in patients with lung cancer. In this study, we examine whether the uptake of [(18)F]fluorodeoxyglucose (FDG), a marker of increased glucose metabolism in neoplastic cells, is of prognostic value in patients with primary lung cancer. METHODS: We have retrospectively analyzed 77 patients (mean age, 63. 0 years; male/female ratio, 53:24) with primary lung cancers who underwent whole body and localized thoracic PET as part of their diagnostic and staging procedures prior to consideration of surgical resection. The standardized uptake value (SUV) of injected FDG for each primary lesion was correlated with tumour histology and the patient's clinical outcome. RESULTS: A SUV of 20 or greater was found to be of significant prognostic value. The chance of survival (with 95% confidence intervals (CI)) at 12 months post-surgery for the various SUV groups was as follows: 75.2% (59.6-85.5) for SUV<10; 67.5% (29.0-88.2) for SUV 10-<12; 63.6% (29.7-84.5) for SUV 12-<15; 66.7% (19.5-90.4) for SUV 15-<20; 16.7% (0.01-0.52) for SUV>20. A SUV of 20 or more is associated with a 4.66 times increase in hazard, compared with lower levels of SUV. We found no significant correlation between tumour histology and SUV. CONCLUSION: We have previously reported on the significant advantages of PET in the staging and surgical care of patients with lung cancer. The present study adds further support for an additional prognostic role for PET in the management of thoracic malignancy as determined by the amount of labelled-FDG taken up by the primary lesion.

Fifth-year hemodynamic performance of the prima stentless aortic valve.

BACKGROUND: The medium-term hemodynamic performance of stentless valves has not been widely reported, particularly in comparison with in vitro studies. Therefore, we have assessed prospectively the hemodynamics of the Edwards Prima valve in its fifth year after implantation in the aortic position, and compared the results with those at 1 month after implantation and also with in vitro data. METHODS: Thirty-five patients (age, 77 +/- 6 years; 19 men) were prospectively studied by Doppler echocardiography at 1 month and 52 +/- 8 months after implantation of a Prima stentless valve. Valve hemodynamics were assessed by measuring the mean pressure gradient, mean valve resistance, and effective orifice area. Left ventricular systolic function was quantified by ejection fraction, the degree of hypertrophy by ventricular mass index, and the ratio of ventricular wall thickness to cavity radius as a measure of ventricular geometry. RESULTS: With a mean valve size of 24.6 +/- 2.2 mm in the fifth year after implantation, the mean pressure gradient was 6.2 +/- 3.5 mm Hg, the mean valve resistance, 29 +/- 16 dyne x s(-1) x cm(-5)), and the effective orifice area was 2.05 +/- 0.50 cm2. Compared with 1 month after operation, there was a 47% decrease in mean valve resistance (p = 0.002) and a 39% increase in effective orifice area (p = 0.001). Furthermore, both effective orifice area and mean valve resistance in the fifth year did not differ from their in vitro counterparts, whereas the left ventricular ejection fraction (0.64 +/- 0.14), the left ventricular mass index (119 +/- 49 g/m2), and the ratio of ventricular wall thickness to cavity radius (0.44 +/- 0.13) were within the normal range. CONCLUSIONS: This study suggests that the Prima valve is a reliable stentless aortic bioprosthesis. This is supported by a favorable medium-term clinical outcome, durable hemodynamic performance, and normal mean values of left ventricular ejection fraction and mass index in the fifth year after implantation.

Studies of vasoactive intestinal polypeptide expression in injured peripheral neurons using capsaicin, sympathectomy and mf mutant rats.

The increased expression of vasoactive intestinal polypeptide (VIP) in injured peripheral neurons was studied. In contrast to substance P, there was a marked increase, and maintained fast axonal transport, of VIP in rat sciatic nerve after peripheral axotomy. Local capsaicin application to the nerve trunk failed to inhibit the injury-induced VIP increase, and capsaicin even increased VIP levels when applied locally to uninjured nerves. Pharmacological sympathectomy showed that some of the peripheral VIP increase may occur in post-ganglionic sympathetic fibres. The VIP increase after injury appeared unaffected in the mf mutant rat, in spite of its loss of lumbar dorsal root ganglion cells. VIP-staining fibres in the epi- and peri-neurium and perivascular plexuses of sciatic nerve showed an increase in number in parallel with the changes of the nerve VIP content. These findings suggest that sensory and sympathetic nerve fibres expressing VIP after injury play a role in the regulation of blood flow to nerves, and in the pathophysiological processes in nerve and dorsal spinal cord which follow peripheral nerve injury.

An increase in the expression of neuropeptidergic vasodilator, but not vasoconstrictor, cerebrovascular nerves in aging rats.

Perivascular nerve fibres containing noradrenaline (NA), serotonin (5-HT), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) were localized in whole-mount stretch preparations of the arteries of the rat circle of Willis using fluorescence and immunohistochemical techniques. Changes in the pattern and density of these perivascular nerves were studied from birth to 27 months of age. All perivascular nerve types reached a peak density of innervation at 1 month of age. This was followed by a general fall in the density of fluorescent nerve fibres. However, with aging, there was a decrease in the expression of vasoconstrictor neurotransmitters (NA and 5-HT) in cerebrovascular nerves, whereas the expression of vasodilator neurotransmitter (VIP and CGRP) in perivascular nerve fibres supplying the rat cerebral arteries was strikingly increased in old age. The density of NPY- and SP-containing nerve fibres was not significantly altered in old age. These changes are discussed in relation to the increased incidence of cerebrovascular disorders in the elderly.

Increased density of perivascular nerves to the major cerebral vessels of the spontaneously hypertensive rat: differential changes in noradrenaline and neuropeptide Y during development.

Fluorescence and immunohistochemical techniques were used to study the pattern and density of perivascular nerves containing noradrenaline (NA) and neuropeptide Y (NPY) supplying the major cerebral arteries of 4-, 6-, 8- and 12-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar (WIS) controls. Levels of NA and NPY in the superior cervical ganglia were measured. The density of nerves containing NA and NPY was greater in the hypertensive animals at all ages studied. However, the developmental changes in the density of innervation showed similar trends in both SHR and WIS groups. With few exceptions, there was a significant increase in the density of nerves containing NA from 4 to 6 weeks and from 8 to 12 weeks of age. This was in contrast to a low expression, and in some vessels a significant decrease in the number of NPY-containing nerves from 4 to 6 weeks. The density of nerve fibres containing NPY increased significantly in almost all vessels between 6 and 8 weeks of age and then stabilized. Thus there is a differential time course for the appearance of NA and NPY during development. Furthermore, the hyperinnervation of cerebral vessels in SHR by nerves containing NA and NPY precedes the onset of hypertension and associated medial hypertrophy. High-performance liquid chromatography and enzyme-linked immunosorbant assays show that the NA and NPY contents of the superior cervical ganglion do not reflect the changes in innervation pattern seen in the terminal fibres in the cerebral arteries. This tends to support the view that a local neurovascular mechanism is involved in the maintenance of hypertension. The possibility that increase in NPY as well as NA in cerebral perivascular nerves of hypertensive animals is involved in the protection of the blood-brain barrier against oedema and cerebral haemorrhage is raised.

Adrenergic innervation of vasa and nervi nervorum of optic, sciatic, vagus and sympathetic nerve trunks in normal and streptozotocin-diabetic rats.

Adrenergic nerves were studied in nervi nervorum and perivascular nerve plexus of vasa nervorum in whole-mount nerve sheath preparations of optic, sciatic and vagus nerves and in the paravertebral sympathetic chain in normal and streptozotocin-treated diabetic rats. A substantial or complete loss of fluorescent adrenergic fibres around blood vessels in the optic nerves was observed 8 weeks after induction of diabetes. This was in marked contrast to the increase in perivascular adrenergic fibres in the sciatic, vagus and sympathetic chain nerve trunks of the same animals at the same time. Assays of noradrenaline levels in whole nerve segments also showed that they were not biochemically detectable in the optic nerves but were significantly higher in the vagus of diabetic animals (P less than 0.05). There was also an increase in numbers of mast cells in the vicinity of vasa nervorum of diabetic nerves.

The nerves to blood vessels supplying blood to nerves: the innervation of vasa nervorum.

Noradrenergic, serotoninergic and peptidergic nerves have been demonstrated in perivascular plexuses of vasa nervorum of sympathetic, parasympathetic and somatic nerve trunks. 5-Hydroxytryptamine-, vasoactive intestinal polypeptide- and substance P-containing fibers were found by immunohistochemistry to variable extents in whole mounts of the epineurium of sciatic, vagus and paravertebral sympathetic chains of rabbits. Innervation increased with age. This suggests an hitherto unsuspected role for these vasoactive substances in normal blood flow to nerves and in the genesis of experimental and human neuropathies.