Assessment of response to beta-blockers by expression of ßArr2 and RhoA/ROCK2 in antrum mucosa in cirrhotic patients.

BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are first choice for prevention of variceal bleeding. But possible deleterious effects in refractory ascites and frequent non-response are clinical drawbacks. Since levels of vasoactive proteins in antrum mucosa reflect vascular dysfunction in cirrhosis, these expression levels might also reflect hemodynamic response to NSBB. METHODS: Biopsies from the gastric and duodenal mucosa of 25 patients with cirrhosis were collected and the hepatic venous pressure gradient (HVPG) was measured before and after an acute propranolol challenge. Transcription and protein expression of Ras homolog family member A (RhoA), Rho-kinase (ROCK)2, beta-arrestin2 (ßArr2), endothelial nitric oxide synthase (eNOS) and the phosphorylation of downstream effectors VASP and moesin were analyzed using PCR and Western blot. Further 21 patients on NSBB were evaluated on their follow up for events of variceal bleeding defined as non-response. RESULTS: Ten patients showed HVPG <10mmHg, further seven patients showed significant hemodynamic response to NSBB, whereas eight patients were non-responders. The mucosal transcription of vasoactive proteins was higher in antrum mucosa compared to corpus and duodenum. The transcriptional levels of vasoactive proteins were higher in patients with HVPG >10mmHg and HVPG >16mmHg. Interestingly, mRNA levels of RhoA and ROCK2 were lower in patients with large varices at endoscopy. Moreover, RhoA and ROCK2 transcription correlated with the decrease of HVPG after acute NSBB challenge. Finally, acute and long-term non-responders showed lower expression of ßArr2 in antrum mucosa. CONCLUSION: This study shows for the first time that the expression of ßArr2 in antrum mucosa biopsies might reflect the hemodynamic response to NSBB and their long-term protective effect. This finding might offer an easy approach at upper endoscopy to facilitate the decision to treat with NSBB if varices are present.

Different injection techniques in the assessment of central haemodynamics in patients with cirrhosis.

OBJECTIVE: Patients with cirrhosis often present with an abnormal distribution of blood volume with a reduced central blood volume (CBV) and central circulation time (CCT). In this group of patients it is important to determine the central haemodynamics as accurately as possible. The purpose of the present study was to compare an alternative injection technique by injecting technetium-labelled human serum albumin ((99m)Tc-HSA) from a deposit within the catheter lumen with the conventional injection technique by injecting iodine-labelled human serum albumin ((125)I-HSA) directly from a syringe. MATERIALS AND METHODS: In 192 patients with cirrhosis, CCT, CBV, and cardiac output (CO) were determined according to kinetic principles. Injection of the two radiolabelled HSA were performed simultaneously and followed by arterial blood sampling every second for the first minute. RESULTS: CCT was significantly shorter, and CO and CBV were significantly lower when determined by the alternative catheter deposit injection technique compared to determination by the traditional syringe deposit injection technique. The mean difference (bias) between CCT measured with the two methods was 0.38 s with limits of agreement ranging from - 0.83 s to 1.59 s. CONCLUSION: This study demonstrates that different injection techniques result in a minor but significant difference of the measured haemodynamics. When highly accurate measurements of the central haemodynamics are needed, we recommend using the alternative injection technique by injection of the indicator from a deposit within the catheter in order to reduce overestimation of CCT.