Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.
Advanced coronary artery disease (CAD) is increasingly common in patients awaiting orthotopic liver transplantation (OLT). Unfortunately, in patients whose coronary artery anatomy is not amenable to angioplasty, coronary artery bypass grafting (CABG) alone may precipitate hepatic decompensation. Thus, combined liver transplant and coronary artery bypass grafting (CABG-OLT) may be required to effectively treat both conditions. Clinical records were analyzed for 5 CABG-OLT procedures at a single institution. Operative indications, technical details, and postoperative course were determined for each patient. Patients undergoing CABG-OLT had a mean age of 57.8 years (range, 54-66) and were predominantly male (80%). All patients had significant 3-vessel coronary atherosclerotic disease with preserved left ventricular function. There were no intraoperative deaths. At mean 25 months of follow-up (range, 8.0-25) there was an 80% graft and patient survival. Overall average length of stay was 21 days (range, 7-59 days). In conclusion, CABG-OLT procedure appears to be safe and effective in the population of patients with advanced CAD and liver disease. In this series, patients appear to benefit from multidisciplinary preoperative evaluation, coordination between cardiac and transplant surgeons, careful graft selection, and use of sapheno-atrial veno-veno bypass.
The influence of assay method on single dose cyclosporine (CsA) pharmacokinetics was studied in nine dogs receiving either i.v. or oral CsA. Samples were drawn from hepatic, portal, and systemic veins at various times after the dose and CsA levels were determined by radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC). Blood concentration-time data were analyzed by nonlinear least-squares regression, using two-compartment models. RIA/HPLC ratios for all samples were greater than one, and did not change significantly over time. The mean RIA/ HPLC ratios for samples drawn from all three veins were higher after oral than i.v. doses of the drug (P<0.05). Area under the concentration-time curve (AUC) was higher and systemic clearance (CIs) lower than calculated on the basis of RIA results, regardless of the route of administration. AUC calculated for CsA metabolites (RIA-HPLC) was highest in the portal vein after an oral dose of CsA. Bioavailability was 20.4% and 27.0% when estimated using HPLC and RIA data, respectively. The mean CsA metabolite index (CMI), when calculated for hepatic, portal, or systemic vein, was greater when the drug was administered orally. The mean hepatic extraction ratio (HER) of the parent drug and for CsA metabolites was approximately 23% in i.v. and p.o. studies. These results suggest that the gastrointestinal tract may play a role in the metabolism of CsA when the drug is administered orally. In addition, if CsA metabolites not measured by HPLC have either toxic or immunosuppressive properties, the RIA assay may be more useful for monitoring patients.The introduction of cyclosporine (CsA) 5 in the immunosuppressive regimen has proven to be the single most important component of success in organ transplantation over the last few years. The drug does not exhibit the bone marrow toxic side effects of immunosuppressive agents used previously, and it exerts selective and reversible inhibition of stimulated T lymphocyte proliferation, apparently by blocking the production of interleukin-2 (1). These advantages are partially offset by the several toxic side effects that have been encountered with increased clinical use of CsA (2,3). Furthermore, it is often difficult to maintain stable The objective of the present study was to understand the significance of the difference between HPLC and RIA measurements of the drug, particularly as it relates to the pharmacokinetics of CsA. The results of the study suggest that there is significant metabolism of the drug by the gastrointestinal tract when administered orally. MATERIALS AND METHODS Experimental proceduresAdult mongrel dogs (weighing 18-22 kg) were used in these studies. The animals were anesthetized and incubated, and the portal vein, a hepatic vein (through the right external jugular vein), and a peripheral vein were cannulated The dogs were allowed to recover from the surgery for 24-48 hr. On the morning of the study, after an overnight fast, a venous blood sample for baseline CsA levels was withdrawn. The animals ...
Arterial and hepatic venous blood levels of glucose were studied in 12 dogs during orthotopic liver transplantation performed under ketamine anesthesia without exogenous glucose administration. During the early part of surgery, arterial blood glucose levels were stable: 161 ± 12 mg/dl (mean ± SEM) after laparotomy and 183 ± 16 Mg/dl 5 min before the anhepatic stage. During the anhepatic stage, arterial blood glucose levels decreased progressively to 135 ± 9 and 88 ± 8 mg/dl, 5 min in the anhepatic stage and 5 min before reperfusion of the graft liver, respectively (P < 0.05). Reperfusion of the graft liver resulted in an increase in arterial glucose levels to 206 ± 17 and 240 ± 24 Mg/dl, 5 and 30 min after reperfusion, respectively (P < 0.05). Hepatic venous blood glucose level increased after reperfusion (405 ± 37 and 346 ± 41 mg/dl, 5 and 30 min after reperfusion, respectively) and Were significantly higher than in arterial blood (P < 0.05). Arterial plasma insulin, measured in five animals, did not change significantly during the procedure, whereas plasma glucagon levels, stable during the preanhepatic and anhepatic stages, increased steadily after reperfusion of the graft liver, from 66.1 ± 14.2 to 108.4 ± 38.1 pg/ml (P < 0.05). This study shows that in dogs with ketamine anesthesia mild hypoglycemia occurs during the anhepatic stage of liver transplantation without exogenous glucose administration followed by hyperglycemia on reperfusion of the graft liver, possibly secondary to the release of glucose from the donor liver.
The ultrastructural distribution of calcium was studied in human lens fibres with the oxalate pyroantimonate technique. In the intermediate cortex precipitates were found perimembranous and occasionally in the fibre cytoplasm. The improved resolution of electron tomography revealed (a) that the perimembranous precipitates as described earlier by Vrensen et al. (1995) are restricted to the intercellular space ; no indications were found of an increased intracellular submembranous calcium level, and (b) the existence of an intracellular pool of small protein attached precipitates in the fibre cytoplasm not observed with conventional electron microscopy. It is concluded that in the intermediate and deep cortex, where in the mature fibres all cellular calcium pools have disappeared, two calcium pools exist : (a) a pool of free calcium ionically bound to the negatively charged phospholipids of the external face of the fibre membrane and (b) a cytoplasmic pool of protein associated calcium. Possible candidates for this cytoplasmic calcium binding are discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.