Changes in the QRS segment during exercise: effects of acute β-blockade with propranolol

Summary. Changes in the QRS complex during exercise may provide information with respect to ischaemic heart disease. The intention with present investigation was to shed light on mechanisms behind QRS changes and to study the possibly confounding effects of β-blockade on such alterations with exercise. Placebo or propranolol respectively was infused in randomized and double-blinded order in seven young healthy men before a maximum exercise test. Advanced computerized vectorcardiography and impedance cardiography was recorded continuously together with blood pressures and blood samples. The Y-lead magnitude increased significantly with propranolol infusion (P<0–05), but it tended to decrease in the Z-lead (P<0.07). While the serum potassium concentrations increased (P< 0.0005), the spatial QRS magnitude tended to decrease irrespective of treatment (P<0.07). These changes correlated with changes in QR-duration (adj r²>0.58). With exercise, the mean spatial QRS magnitude decreased with similar amounts irrespective of treatment. However, propranolol made the magnitude decrease earlier (P<001). No effect of treatment was detected on the decrease in QRS-duration. Immediately after exercise, the QRS complex continued to change as during exercise in the placebo investigations, but did not with propranolol (P<0.05). These different patterns were most obvious in the first half of the QRS complex in the Y-lead. It is concluded that acute β-blockade modifies QRS alterations both during and after exercise in healthy subjects. This indicates that such drugs may have confounding effects in evaluations of the diagnostic value of QRS alterations.     

Effects of acute carbohydrate administration on central and peripheral hemodynamic responses to mental stress.

Essential hypertension is closely related to conditions with impaired glucose tolerance and hyperinsulinemia. To evaluate a possible interaction between the sympathetic nervous system and carbohydrate ingestion on the circulatory responses to psychosocial stress, we compared the hemodynamic effects of an oral glucose challenge with those observed after placebo in 10 glucose-tolerant, normotensive young men at rest and during standardized mental stress. After glucose, resting cardiac output increased by 20% (p less than 0.05), which was mainly due to an increased heart rate (+14%; p less than 0.001). Since total peripheral resistance decreased by 13% (p less than 0.02), mean arterial pressure was unaffected by glucose. In spite of this, glucose loading was associated with a slight increase in systolic blood pressure and a gradual decrease of diastolic blood pressure. Resting forearm blood flow was unaffected by glucose. The stress response after placebo was characterized by the expected increase in cardiac output and mean arterial pressure, and an unchanged total peripheral resistance. By contrast, in the postprandial state the pressor response to stress was solely dependent on an increased systemic vascular resistance, and cardiac output was unaffected by stress. After glucose, the stress-induced muscular vasodilation in the forearm was reduced to 40% of that observed after placebo (p less than 0.01). Thus, acute carbohydrate administration has significant hemodynamic effects in humans. Furthermore, during the postprandial period there is a marked alteration of the pattern of the circulatory responses to psychosocial stress, characterized by attenuated muscular vasodilation and a rise in systemic vascular resistance.     

The expression of NAD(P)H:quinone oxidoreductase 1 is high in human adipose tissue, reduced by weight loss, and correlates with adiposity, insulin sensitivity, and markers of liver dysfunction

CONTEXT: We have previously identified nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 (NQO1), an enzyme involved in the protection against oxidative stress, as a gene predominantly expressed in human adipocytes. Studies in mice deficient in NQO1 activity suggest that NQO1 may also play an important role in metabolism. OBJECTIVE: The aim of this study was to explore the expression and regulation of NQO1 in human adipose tissue (AT) and isolated adipocytes. PATIENTS AND RESULTS: The high expression of NQO1 in adipocytes was verified in human adipocytes and AT by real-time PCR. DNA microarray analysis showed that NQO1 was expressed at higher levels in large compared with small adipocytes, isolated from the same fat biopsy. Furthermore, NQO1 mRNA levels were positively correlated with adipocyte size (n = 7; P < 0.002). During an 18-wk diet regime (n = 24; mean weight loss 27 kg), the NQO1 expression in human sc AT was down-regulated (P < 0.0001), and mRNA levels correlated with body mass index (P = 0.0005), sc, and total abdominal AT areas, as determined by computerized tomography (P < 0.0001, both) and metabolic parameters. NQO1 mRNA levels were also positively correlated with aspartate aminotransferase (P = 0.0028) and alanine aminotransferase (P = 0.0219), markers known to be associated with severity of hepatic steatosis. CONCLUSIONS: NQO1 is highly expressed in human AT, particularly in large adipocytes. AT NQO1 expression is reduced during diet-induced weight loss, and the expression levels positively correlate with adiposity, glucose tolerance, and markers of liver dysfunction. Together, these findings indicate a role for NQO1 in the metabolic complications of human obesity.     

The autocrine motility factor receptor is overexpressed on the surface of B cells in Binet C chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a clinical spectrum reaching from discrete lymphocytosis to extensive enlargement of lymph nodes, spleen and liver, and bone marrow failure. The aim of this study was to identify genes that differentiate between patients with disease stage A vs. C according to Binet in order to better understand the disease. To achieve this, we performed DNA microarray analysis on B cells from CLL patients with stage A and C according to Binet and matched controls. Between CLL patients and controls, there were 1,528 differentially expressed genes and 360 genes were differentially expressed between Binet A and C patients. Due to the sheer number of regulated genes, we focused on the autocrine motility factor receptor (AMFR). AMFR has not previously been investigated in hematological disorders, but high expression of AMFR correlates with a more advanced stage and invasive potential in several human tumors. AMFR mRNA expression was higher in Binet A compared with Binet C patients (P = 0.0053) and healthy controls (P = 0.0051). Total AMFR protein was higher in Binet A patients compared to Binet C as analyzed by intracellular flow cytometry. However, AMFR exist both in the ER involved in protein degradation and on the cell surface involved in metastasis and cell motility. Cell surface AMFR was increased in Binet C compared with Binet A + B (P = 0.016). In conclusion, the mRNA levels reflect the total amount of AMFR, whereas cell surface expression is associated with progression in CLL.