A perspective on cirrhotic cardiomyopathy.

Cardiac dysfunction in patients with cirrhosis and potential clinical implications have long been known, but the pathophysiology and potential targets for therapeutic intervention are still under investigation and are only now becoming understood. The pathophysiological changes result in systolic dysfunction, diastolic dysfunction, and electrophysiological changes. Here, we aim to review cirrhotic cardiomyopathy from a cellular and physiological model and how these patients develop overt heart failure in the setting of stress, such as infection, ascites, and procedures including transjugular intrahepatic portosystemic shunt, portocaval shunts, and orthotopic liver transplantation. We will also review the most current, although limited, available therapeutic modalities.

Reversible cardiomyopathies--a review.

End-stage renal disease, cirrhosis, obesity, tachycardia, and extreme stress have all been shown to result in impaired left ventricular function. It is becoming clear, however, that the cardiomyopathies associated with these states are reversible after resolution of the underlying process. In this article, we present the current data demonstrating that renal transplantation, liver transplantation, and bariatric surgery can lead to reversal of uremic, cirrhotic, and obesity cardiomyopathies, respectively. We also discuss the reversibility of tachycardia-induced cardiomyopathy after radiofrequency ablation or pharmacologic therapy for rate or rhythm control and the reversibility of stress-induced cardiomyopathy with supportive care.

Severe left ventricular systolic dysfunction may reverse with renal transplantation: uremic cardiomyopathy and cardiorenal syndrome.

Chronic heart failure (CHF) and chronic kidney disease (CKD) are serious medical conditions with significant morbidity and mortality. Emerging evidence indicates that the function of these two organ systems are affected by each other in a complex interplay. Most patients with CKD suffer frequently from cardiac abnormalities including left ventricular hypertrophy (LVH), left ventricular dilatation (LVD), left ventricular (LV) diastolic and/or systolic dysfunction. Although previously thought that LV systolic dysfunction was an absolute contraindication to renal transplantation, several observational studies have shown this not to be true and that transplantation can lead to significant improvement in LV systolic function. Furthermore, correction of the uremic state by renal transplantation leads to improvement of LVD and possibly regression of LVH. In fact, the reduction of LVH postkidney transplantation was shown to be dependent on adequate renal function and hypertension control. Diabetes mellitus does not seem to be a confounding factor in the improvement of uremic cardiomyopathy with renal transplantation.

Characterization of phosphate residues on thyroglobulin.

Follicular 19 S thyroglobulin (molecular weight 660,000) from rat, human, and bovine thyroid tissues contains approximately 10-12 mol of phosphate/mol of protein. These phosphate residues can be radiolabeled when rat thyroid hemilobes, FRTL-5 rat thyroid cells, or bovine thyroid slices are incubated in vitro with [32P]phosphate. Thus labeled, the [32P]phosphate residues comigrate with unlabeled 19 S follicular thyroglobulin on sucrose gradients and gel filtration columns; are specifically immunoprecipitated by an antibody preparation to rat or bovine thyroglobulin as appropriate; and co-migrate with authentic 19 S thyroglobulin when subjected to analytic or preparative gel electrophoresis. Tunicamycin prevents approximately 50% of the phosphate from being incorporated into FRTL-5 cell thyroglobulin. Approximately one-half of the phosphate in FRTL-5 cell or bovine thyroglobulin can also be released by enzymatic deglycosylation and can be located in Pronase-digested peptides which contain mannose, are endo-beta-N-acetylglucosaminidase H but not neuraminidase-sensitive, and release a dually labeled oligosaccharide containing mannose and phosphate after endo-beta-N-acetylglucosaminidase H digestion. The remainder of the phosphate is in alkali-sensitive phosphoserine residues (3-4/mol of protein) and phosphotyrosine residues (approximately 2/mol of protein). This is evidenced by electrophoresis of acid hydrolysates of 32P-labeled thyroglobulin and by reactivity with antibodies directed against phosphotyrosine residues. The phosphoserine and phosphotyrosine residues do not appear to be randomly located through the thyroglobulin molecule since approximately 75-85% of the phosphotyrosine and phosphoserine residues were recovered in a approximately 15-kDa tryptic peptide or a approximately 24-kDa cyanogen bromide peptide, each almost devoid of carbohydrate. 31P nuclear magnetic resonance studies of bovine thyroglobulin confirm the presence and heterogeneity of the phosphate residues on thyroglobulin preparations.