AF in humans leads to important changes in atrial potassium and calcium currents that likely contribute to the decrease in APD and APD rate adaptation. These changes contribute to electrical remodeling in AF and are therefore important factors for the perpetuation of the arrhythmia.

Chronic AF in humans reduces Ito by transcriptional down-regulation of the Kv4.3 potassium channel. Altered gene expression is an important component of the electrical remodeling process and may contribute to repolarization abnormalities in AF.

Molecular and electrical remodeling of ion channels determining action potential duration has been proposed as a major mechanism in chronic atrial fibrillation. We investigated the mRNA expression of the cardiac L-type Ca2+-channel subunits alpha1c, alpha2/delta1, beta1a, and beta1b/c in atrial tissue of patients with chronic atrial fibrillation compared to patients in sinus rhythm. In addition, the mRNA expression of the 5-hydroxytryptamine type 4-, beta1-, and beta2-adrenergic receptors, which are known to stimulate the L-type Ca2+-current in human atrium, was analyzed and the effect of chronic beta-blocker treatment on the mRNA expression of these receptors and of the L-type Ca2+-channel subunits was assessed. Total RNA was isolated from right atrial appendages of patients in sinus rhythm and of patients with chronic atrial fibrillation. Then, semiquantitative RT-PCR using 18S RNA as the "housekeeping gene" was performed. In patients with chronic atrial fibrillation, there were only mild reductions in mRNA expression of the alpha1c-subunit (-15.5 %, p = 0.13), and of the beta1-subunit isoforms a and c (-13.3 %, p = 0.14 and -16.6%, p = 0.18, respectively). However, mRNA expression of the alpha2/delta1-subunit (-31.5 %, p < 0.01) and of the beta1-subunit isoform b (-39.9 %, p < 0.0005) was significantly reduced in patients with chronic AF. Taken together, the mRNA expression of the beta1-subunit isoforms b and c, which are splice variants, was significantly down-regulated by 26.5 % (p < 0.05) in these patients. The analysis of the beta1c/beta1b ratio resulted in a significant shift by 39.2 % (p < 0.0001) in favor of beta1c in patients with chronic atrial fibrillation. In the AF patients, the abundance of the 5-HT4-receptor transcript was significantly reduced by 36 % (p < 0.05). The beta-adrenoreceptor transcription was unchanged. In both SR and AF patients, chronic beta-blocker treatment did neither significantly effect the mRNA expression of the L-type Ca2+-channel subunits, the beta-adrenoreceptor subtypes 1 and 2, nor that of the 5-HT4-receptor. Our data show that chronic AF is associated with a decrease in the atrial mRNA amount of auxiliary subunits of the L-type Ca2+-channel and of the 5-HT4-receptor. This supports the hypothesis that the observed alterations in mRNA transcription in AF patients may lead to a decrease in the availability of functional L-type Ca2+-channels and 5-HT4-receptors and/or reduce L-type Ca2+-current amplitude and density, thus, promoting and stabilizing the arrhythmia.

We have developed a rat CPB with mild hypothermic cardioplegic arrest. This rodent model is suitable to study clinically relevant problems related to CPB,myocardial protection and systemic inflammation.

The current study suggests that the major -863 CC variant determines elevated TNF-α level preoperatively and throughout the postoperative course after CPB.

Background: Ciprofloxacin (CFLX) is a fluoroquinolone antibiotic with a broad antimicrobial spectrum. This study was performed to examine the retinal toxicity of free and liposome-incorporated CFLX in rabbit eyes after intravitreal injection. Materials and Methods: Free CFLX in doses of 100, 250, 500, 1,000 and 2,000 µg was injected into the midvitreous of rabbit eyes (n = 28). To prolong the intravitreal antibacterial level, CFLX was incorporated into multilamellar liposomes: 0.1 ml of this suspension (≙ 273.6 µg CFLX) was injected into the midvitreous of a second group of rabbit eyes (n = 6). The other eye served as a control and received normal saline solution or empty liposomes, respectively. Before injection and at the end of follow-up an electroretinogram (ERG) was obtained. After a follow-up of 1, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light and transmission electron microscopy. Results: Significant reduction of the ERG was observed after 2,000 µg free CFLX in 4 out of 6 eyes after 14 days. Fourteen days after injection of 2,000 µg CFLX the central retina showed pigmentary changes in 4 out of 6 eyes. In the second group the ERG as well as the histologic studies did not reveal any pathologic changes after injection of liposome-incorporated CFLX compared to the control eyes. Conclusion: In therapeutic doses of 100–500 µg, free CFLX does not have retinal toxicity in rabbit eyes. No retinal toxicity was observed after intravitreal injection of liposome-incorporated CFLX.

No abstract

Objectives: Acute kidney injury following cardiac surgery depicts a severe clinical problem that is strongly associated with adverse short-and long-term outcome. We analyzed two common genetic polymorphisms that have previously been linked to renal failure and inflammation, and have been supposed to be associated with cardiac surgery associated-acute kidney injury (CSA-AKI). Methods: A total of 1415 consecutive patients who underwent elective cardiac surgery with CPB at our institution were prospectively enrolled. Patients were genotyped for Apolipoprotein E (ApoE E2,E3,E4) (rs429358 and rs7412) and TNF-a-308 G4A (rs1800629). Results: Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between ApoE (E2,E3,E4) and TNF-a-308 G4A genotypes and the RIFLE criteria could be detected. Several multiple linear regression analyses for postoperative creatinine increase revealed highly significant associations for aortic cross clamp time (p50.001), CPB-time (p50.001), norepinephrine (p50.001), left ventricular function (p ¼ 0.004) and blood transfusion (p50.001). No associations were found for ApoE (E2,E3,E4) and TNF-a-308 G4A genotypes or baseline creatinine. When the sample size is 1415, the multiple linear regression test of R 2 ¼ 0 for seven covariates assuming normal distribution will have at least 99% power with significance level 0.05 to detect an R 2 of 0.108 or 0.107 as observed in the data. Conclusions: ApoE (E2,E3,E4) polymorphism and the TNF-a-308 G4A polymorphism are not associated with renal injury after CPB.