Compensatory Thrombopoietin Production from the Liver and Bone Marrow Stimulates Thrombopoiesis of Living Rat Megakaryocytes in Chronic Renal Failure

Background/Aims: Decreased thrombopoiesis has been ascribed a role in the pathogenesis of uremic bleeding in chronic renal failure (CRF). However, serum thrombopoietin (TPO) levels are usually elevated in CRF patients, suggesting increased thrombopoiesis. The aim of this study was to determine the thrombopoietic activity in CRF. Methods: Male Sprague-Dawley rats that underwent 5/6 nephrectomy were used as the model of CRF. Age-matched sham-operated rats were used as controls. Single megakaryocytes were isolated from the rat bone marrow, and their size distribution was examined. Megakaryocyte membrane invaginations were monitored by confocal imaging of di-8-ANEPPS staining, and patch clamp whole-cell recordings of membrane capacitance. TPO gene expression was assessed in various tissues. Results: Circulating platelet counts and the number of large megakaryocytes were increased in the bone marrow of CRF rats. Massive di-8-ANEPPS staining and increased membrane capacitance in large megakaryocytes demonstrated increased membrane invaginations. Unaffected Kv1.3-channel currents per cell surface area demonstrated unaltered channel densities. TPO transcription was decreased in the renal cortex but increased in the liver and bone marrow of CRF rats. Conclusion: Increased thrombopoiesis in CRF was thought to be a reactive mechanism to platelet dysfunction. Increased TPO production from the liver and bone marrow compensated for decreased production from damaged kidneys

Anesthetic management in an adult moyamoya disease patient undergoing mitral valve plasty for severe mitral regurgitation

Abstract Background Despite several previous reports, there are no established procedures for intraoperative management in moyamoya disease patients requiring cardiac surgery. Case presentation Herein, we report the case of a 42-year-old man who was scheduled to undergo mitral valve plasty for severe mitral regurgitation. He had been diagnosed with moyamoya disease on the onset of cerebral ischemia at 41 years of age. During the cardiac surgical procedure, the patient was maintained on inhalation anesthesia with 1 to 1.5 % sevoflurane. Sevoflurane causes cerebral vasodilation followed by increased cerebral blood flow, and moreover we expected a sevoflurane preconditioning-induced neuroprotective effect. In addition, we used pulsatile perfusion support to maintain cerebral circulation with intra-aortic balloon pumping during the cardiopulmonary bypass. We aimed to keep the mean arterial pressure constantly above 70 mmHg. We were able to maintain regional cerebral oxygen saturation at 80 % of the baseline value, and could not detect the progression of neurological deficits using follow-up brain single photon emission computed tomography. The patient was discharged 16 days after admission. Conclusions The details of the clinical course of his case will add to our knowledge regarding intraoperative management options in moyamoya disease patients requiring cardiac surgery. We suggest that pulsatile blood flow supported by intra-aortic balloon pumping and sevoflurane anesthesia for increasing cerebral blood flow and for possible neuroprotection may be efficacious for anesthetic management of moyamoya disease patients

Implantation of ventricular assist device for systemic right ventricular failure in a patient with transposition of the great arteries and post-Mustard procedure: a case report

Abstract Background Ventricular assist device (VAD) is usually attached by an inflow cannula to the apex of the systemic left ventricle (LV), but very few cases with implantation of the VAD in the morphologic right ventricle (RV) have been described. Case presentation We describe the case of a 41-year-old male who developed severe systemic RV failure related to a Mustard procedure he had as an infant for treatment of TGA. His heart failure was refractory and irreversible, and therefore, he underwent VAD implantation for systemic RV support. Although the patient developed pulmonary congestion on postoperative day (POD) 5, he was discharged on POD 60. He is now looking forward to receiving heart transplantation. Conclusions Placement of a VAD for systemic RV failure could be a life-saving treatment in adult patients with heart failure due to congenital heart disease

Salicylate Inhibits Thrombopoiesis in Rat Megakaryocytes by Changing the Membrane Micro-Architecture

Background/Aims: Salicylate causes drug-induced immune thrombocytopenia. However, some clinical studies indicate the presence of additional mechanisms in the drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. Since salicylate is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate on the membrane capacitance in rat megakaryocytes. Taking electron microscopic imaging of the cellular surface, we also examined the effects of salicylate on the membrane micro-architecture of megakaryocytes. Results: Salicylate significantly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging technique. As shown by electron microscopy, salicylate actually halted the process of pro-platelet formation in megakaryocytes. Conclusion: This study demonstrated for the first time that salicylate inhibits the process of thrombopoiesis in megakaryocytes, as detected by the decrease in the membrane capacitance. Salicylate-induced changes in the membrane micro-architecture are thought to be responsible for its effects