The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2021 Part II: Cardiac Transplantation.

This article spotlights the research highlights of this year that specifically pertain to the specialty of anesthesia for heart transplantation. This includes the research on recent developments in the selection and optimization of donors and recipients, including the use of donation after cardiorespiratory death and extended criteria donors, the use of mechanical circulatory support and nonmechanical circulatory support as bridges to transplantation, the effect of COVID-19 on heart transplantation candidates and recipients, and new advances in the perioperative management of these patients, including the use of echocardiography and postoperative outcomes, focusing on renal and cerebral outcomes.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2021.

This special article is the fourteenth in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the Editor-in-Chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series; namely, the research highlights of the past year in the specialty of cardiothoracic and vascular anesthesiology. The major themes selected for 2021 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights in the specialty for 2021 begin with an update on structural heart disease, with a focus on updates in arrhythmia and aortic valve disorders. The second major theme is an update on coronary artery disease, with discussion of both medical and procedural management. The third major theme is focused on the perioperative management of patients with COVID-19, with the authors highlighting literature discussing the impact of the disease on the right ventricle and thromboembolic events. The fourth and final theme is an update in heart failure, with discussion of diverse aspects of this area. The themes selected for this fourteenth special article are only a few of the diverse advances in the specialty during 2021. These highlights will inform the reader of key updates on a variety of topics, leading to improvement of perioperative outcomes for patients with cardiothoracic and vascular disease.

Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity.

BACKGROUND: Multiple myeloma is a cancer of plasma cells that often leads to complications including osteolytic bone lesions, nephropathy and neuropathy. Multiple myeloma is only one etiology of many cancer pain conditions that may necessitate interventional pain treatment when refractory to multimodal medications. Notably, local anesthetic systemic toxicity is a rare but life-threatening complication of local anesthetic administered for these interventions. CASE PRESENTATION: A 50-60-year-old woman presented with multiple myeloma complicated by chronic bone pain and in an acute pain crisis. A fluoroscopic-guided L4-5 epidural catheter was placed with clinical doses of bupivacaine for comfort to undergo MRI of the spine. Soon after, she became tachycardic, tachypneic and hypoxic requiring non-invasive positive pressure airway support. As this respiratory distress was attributed to a large pleural effusion, a pigtail catheter was inserted in the intensive care unit with submaximally dosed lidocaine infiltration. She then developed a left bundle branch block followed by cardiovascular collapse minimally responsive to high-dose inotrope and vasopressor support. Lipid emulsion was started with dramatic therapeutic response and recovery to baseline. A CT of the thoracolumbar spine showed worsening extensive lytic lesions throughout all vertebral bodies and ribs from diffuse myeloma. CONCLUSIONS: Patients with oncologic lesions focal to the thoracolumbar spine may be at higher risk for local anesthetic systemic toxicity from palliative epidurals due to increased cancer-related angiogenesis. Likewise, local anesthetic infiltration for procedures near any malignant sites could have a similar risk and may require lower initial fractionated dosages with increased vigilance.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2020.

THIS SPECIAL article is the 13th in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr Kaplan, and the editorial board for the opportunity to continue this series; namely, the research highlights of the past year in the specialty of cardiothoracic and vascular anesthesiology.1 The major themes selected for 2020 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights in the specialty for 2020 begin with an update on valvular disease, with a focus on updates in management of aortic and mitral valve disorders. The second major theme is an update on coronary artery disease, with discussion of both medical and surgical management. The third major theme is focused on the perioperative management of patients with coronavirus disease 2019 (COVID-19), with the authors highlighting literature discussing medical, surgical, and anesthetic considerations for their cardiac care. The fourth major theme is an update in heart failure, with discussion of medical, psychosocial, and procedural aspects of this complicated disease process. The fifth and final theme focuses on the latest analyses regarding survival in heart transplantation. The themes selected for this 13th special article are only a few of the diverse advances in the specialty during 2020. These highlights will inform the reader of key updates on a variety of topics, leading to improvement of perioperative outcomes for patients with cardiothoracic and vascular disease.

Cannulation strategies in adult veno-arterial and veno-venous extracorporeal membrane oxygenation: Techniques, limitations, and special considerations.

Extracorporeal membrane oxygenation (ECMO) refers to specific mechanical devices used to temporarily support the failing heart and/or lung. Technological advances as well as growing collective knowledge and experience have resulted in increased ECMO use and improved outcomes. Veno-arterial (VA) ECMO is used in selected patients with various etiologies of cardiogenic shock and entails either central or peripheral cannulation. Central cannulation is frequently used in postcardiotomy cardiogenic shock and is associated with improved venous drainage and reduced concern for upper body hypoxemia as compared to peripheral cannulation. These concerns inherent to peripheral VA ECMO may be addressed through so-called triple cannulation approaches. Veno-venous (VV) ECMO is increasingly employed in selected patients with respiratory failure refractory to more conventional measures. Newer dual lumen VV ECMO cannulas may facilitate extubation and mobilization. In summary, the pathology being addressed impacts the ECMO approach that is deployed, and each ECMO implementation has distinct virtues and drawbacks. Understanding these considerations is crucial to safe and effective ECMO use.

A dynamic equilibrium between CDKs and PP2A modulates phosphorylation of pRB, p107 and p130.

It is thought that G(1) cyclin/CDK mediated phosphorylation of pocket proteins from mid G(1) to mitosis is reversed via dephosphorylation in mitosis. We examined the mechanisms involved in the unexpectedly rapid dephosphorylation of the pocket proteins induced via inhibition of cellular protein synthesis by cycloheximide (CHX) as well as direct inhibition of CDKs by flavopiridol. CHX and flavopiridol-induced dephosphorylation of pocket proteins is attributable to inactivation of D-type cyclin/CDKs and G(1)/S CDKs, respectively, which unmasks a phosphatase activity that targets the three pocket proteins apparently throughout the cell cycle. Treatment of cells with phosphatase inhibitors at concentrations selective for PP2A inhibition prevents CHX and flavopiridol-mediated dephosphorylation of pocket proteins in vivo. Also, ectopic expression of SV40 small t antigen, which inhibits PP2A via disruption of trimeric PP2A holoenzymes, delays CHX-induced pocket protein dephosphorylation. Moreover, dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit PP2A, but not PP1. Finally, the PP2A catalytic subunit (PP2A/C) specifically interacts with both p130 and p107 in quiescent cells as well as cells progressing throughout the cell cycle. Together, these results demonstrate that the overall phosphorylation state of pocket proteins is determined, at least in part, by a dynamic equilibrium between CDKs and PP2A, or a closely related PP2A-like enzyme. These findings have important implications, as cell cycle or checkpoint-dependent inhibition of CDK activities counteracted by an active PP2A should have imminent effects on the phosphorylation state and activities of pocket proteins.

4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin.

To determine whether inhibition of either the ribosomal p70 S6 kinase or eukaryotic initiation factor (eIF) 4E pathways downstream of the mammalian target of rapamycin, mTOR, contributes to rapamycin-induced growth arrest, clones of Rh30 rhabdomyosarcoma cells were selected for rapamycin resistance. Expression of c-Myc and anchorage-independent growth were enhanced in resistant cells. Resistance was unstable in each of three clones characterized. In resistant cells, as compared with parental cells, approximately 10-fold less 4E-binding protein (4E-BP) was bound to eIF4E, and total cellular 4E-BP was markedly reduced. Levels of eIF4E were unchanged. Steady-state levels of 4E-BP transcript remained unaltered, but the rate of 4E-BP synthesis was reduced in resistant cells. In cells that reverted to rapamycin sensitivity, levels of total 4E-BP returned to those of parental cells. Compared with parental cells, resistant clones had either similar or lower levels and activity of ribosomal p70 S6 kinase, but c-Myc levels were elevated in both resistant and revertant clones. Several colon carcinoma cell lines with intrinsic rapamycin resistance were found to have low 4E-BP:eIF4E ratios. In stable clones of HCT8 carcinoma engineered to overexpress 4E-BP, rapamycin sensitivity increased markedly (>1000-fold) as 4E-BP expression increased. These results suggest that the 4E-BP:eIF4E ratio is an important determinant of rapamycin resistance and controls certain aspects of the malignant phenotype.