Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end-stage heart failure

There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8; ventricle, n=14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT1R. Stringent conditions were used for both hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT1R mRNA may occur in response to elevated atrial pressures in heart failure.     

Production of anti-erythrocyte antibodies by leukemic and nonleukemic B cells in chronic lymphocytic leukemia patients

We have assessed the specificity of antibodies from the leukemic B cells of five patients with both chronic lymphocytic leukemia and autoimmune hemolytic anemia (CLL-AHA). Leukemic cells from one patient displayed surface immunoglobulin with heavy and light chain isotypes identical to that of the patient's anti-red blood cell (RBC) antibodies, and the leukemic cells secreted antibodies in vitro with anti-RBC activity. However, in the remaining patients, the leukemic cells displayed surface immunoglobulin with light chain isotypes different from that of the patient's anti-RBC antibodies and secreted antibodies in vitro with no detectable anti-RBC activity. Thus, there are two distinct classes of CLL-AHA patients, differentiated by the presence or absence of an anti-RBC antibody-producing leukemic B cell clone. The apparent heterogeneity in the source of pathogenic anti-RBC antibodies may impact the treatment response of the two classes of CLL-AHA patients.     

Localization of dopamine1A receptor mRNA in different vascular beds in rat: a nonradioactive in situ hybridization study

In situ hybridization of a biotin-labeled specific dopamine1A (D1A) receptor gene oligonucleotide probe combined with computer-assisted image analyzer was used to directly visualize D1A receptor mRNA and quantify the relative mRNA levels in sections of rat aorta and pulmonary and caudal arteries. Positive D1A receptor mRNA signals were found in rat aorta and pulmonary arteries, while no specific signals could be detected in the caudal artery. D1A receptor mRNA was located mainly within the medial layer of aorta, with intimal distribution in the pulmonary artery. The density of D1A receptor mRNA in different vascular beds demonstrated heterogeneity. D1A receptor mRNA levels in the aorta were much higher than those in the pulmonary artery (p < 0.01). These results demonstrate the existence of D1A receptor mRNA in both aorta and pulmonary beds, although with different distribution and density. The results further support the heterogeneity of the D1A receptor in different vascular beds.     

No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats

Background

Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr) could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR).

Findings

Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 ± 1.5 vs. Pl: 12.2 ± 1.7 nmol·mg^-1; p = 0.87), heart (Cr: 11.5 ± 1.8 vs. Pl: 14.6 ± 1.1 nmol·mg^-1; p = 0.15), plasma (Cr: 67.7 ± 9.1 vs. Pl: 56.0 ± 3.2 nmol·mg^-1; p = 0.19), plantaris (Cr: 10.0 ± 0.8 vs. Pl: 9.0 ± 0.8 nmol·mg^-1; p = 0.40), and EDL muscle (Cr: 14.9 ± 1.4 vs. Pl: 17.2 ± 1.5 nmol·mg^-1; p = 0.30). Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p > 0.05).

Conclusions

Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension.     

Seroprevalence survey of Egyptian tourism workers for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum infections: association of hepatitis C virus infections with specific regions of Egypt

Blood samples from 740 Egyptian Nationals working in the tourism industry at two sites in the South Sinai governorate were screened for markers of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Treponema pallidum. Study subjects included 467 individuals from a rural seashore tourist village and 273 persons at two hotels in a well-established resort town. Subjects' ages ranged from 15 to 70 years; 99.3% were male. The prevalence of serologic markers for currently asymptomatic or past HBV infection alone was 20.7% (n = 153), of markers for past or chronic HCV infection alone was 7.4% (n = 55), and of markers for both HBV and HCV was 6.9% (n = 51). Of the 204 individuals positive for anti-HBV core antibody, 12 (5.9%) were also positive for hepatitis B surface antigen. Two individuals (0.3%) had a serologic market suggestive of an active syphilitic infection. No subject was found to be HIV-seropositive. History of prior injections and number of injections were associated with infection with HCV. Primary residence in the Nile delta and valley areas where schistosomiasis is highly endemic, was also a statistically significant risk factor for HCV, but not HBV infection.     

The effect of changing excitation frequency on parallel conductance in different sized hearts

OBJECTIVE: An important component of the ventricular volume measured using the conductance catheter technique is due to parallel conductance (Vc), which results from the extension of the electric field beyond the ventricular blood pool. Parallel conductance volume is normally estimated using the saline dilution method (Vc(saline dilution)), in which the conductivity of blood in the ventricle is transiently increased by injection of hypertonic saline. A simpler alternative has been reported by Gawne et al. [12]. Vc(dual frequency) is estimated from the difference in total conductance measured at two exciting frequencies and the method is based on the assumption that parallel conductance is mainly capacitive and hence is negligible at low frequency. The objective of this study was to determine whether the dual frequency technique could be used to substitute the saline dilution method to estimate Vc in different sized hearts. METHODS: The accuracy and linearity of a custom-built conductance catheter (CC) system was initially assessed in vitro. Subsequently, a CC and micromanometer were inserted into the left ventricle of seven 5 kg pigs (group 1) and six 50 kg pigs (group 2). Cardiac output was determined using thermodilution (group 1) and an ultrasonic flow probe (group 2) from which the slope coefficient (alpha) was determined. Steady state measurements and Vc estimated using saline dilution were performed at frequencies in the range of 5-40 kHz. All measurements were made at end-expiration. Finally, Vc was estimated from the change in end-systolic conductance between 5 kHz and 40 kHz using the dual frequency technique of Gawne et al. [12]. RESULTS: There was no change in measured volume of a simple insulated cylindrical model when the stimulating frequency was varied from 5-40 kHz. Vc(saline dilution) varied significantly with frequency in group 1 (8.63 +/- 2.74 ml at 5 kHz; 11.51 +/- 2.65 ml at 40 kHz) (p = 0.01). Similar results were obtained in group 2 (69.43 +/- 27.76 ml at 5 kHz; 101.24 +/- 15.21 ml at 40 kHz) (p < 0.001). However, the data indicate that the resistive component of the parallel conductance is substantial (Vc at 0 Hz estimated as 8.01 ml in group 1 and 62.3 ml in group 2). There was an increase in alpha with frequency in both groups but this did not reach significance. The correspondence between Vc(dual frequency) and Vc(saline dilution) methods was poor (group 1 R2 = 0.69; group 2 R2 = 0.22). CONCLUSION: At a lower excitation frequency of 5 kHz a smaller percentage of the electric current extends beyond the blood pool so parallel conductance is reduced. While parallel conductance is frequency dependent, it has a substantial resistive component. The dual frequency method is based on the assumption that parallel conductance is negligible at low frequencies and this is clearly not the case. The results of this study confirm that the dual frequency technique cannot be used to substitute the saline dilution technique.     

Recurrent polymorphic ventricular tachycardia complicating radiofrequency catheter ablation of the atrioventricular junction

Recurrent ventricular tachycardia and ventricular fibrillation were observed immediately after RF ablation of the AV junction in a 64-year-old man. This arrhythmia was preceded by ventricular bigeminy and a long-short sequence. It was not associated with prolongation of the QT interval compared to baseline, and recurred 3 months later despite ventricular pacing at 90 beats/min. This is the first reported case of sustained ventricular arrhythmia complicating RF AV junction ablation despite rapid ventricular pacing, and recurring 3 months after discharge. It may explain the rare cases of sudden death complicating this procedure.