Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.

The diversity among cyclic nucleotide phosphodiesterases provides multiple mechanisms for regulation of cAMP and cGMP in the cardiovascular system. Here we report that a calmodulin-stimulated phosphodiesterase (PDE1C) is highly expressed in proliferating human arterial smooth muscle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta. High levels of PDE1C were found in primary cultures of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the major cAMP hydrolytic activity in these SMCs. PDE expression patterns in primary SMC cultures from monkey and rat aortas were different from those from human cells. In monkey, high expression of PDE1B was found, whereas PDE1C was not detected. In rat SMCs, PDE1A was the only detectable calmodulin-stimulated PDE. These findings suggest that many of the commonly used animal species may not provide good models for studying the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs suggests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplasty, conditions in which proliferation of arterial SMCs is negatively modulated by cyclic nucleotides.     

Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml^-1 or < 300 ng.ml^-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127–141 [120–172]) g.l^-1, 143 (133–150 [120–179]) g.l^-1, p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77–82 [9–85]) days vs. 81 (79–83 [0–85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.     

Isolation and identification of chondroitin sulfates from the mud snail

Chondroitin sulfates were isolated from the mud snail. For the quantitative analysis of enzymatic digestion products of isolated chondroitin sulfates, strong anion exchange-high performance liquid chromatography (SAX-HPLC) was performed. By the action of chondroitinase ABC, three unsaturated disaccharides 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-D-galactose (ΔDi-OS), 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (ΔDi-6S) and 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (ΔDi-4S) were produced from the mud snail chondroitin sulfates. The analysis showed that relative proportion of ΔDi-OS/ΔDi-6S/ΔDi-4S was 58.7/3.1/38.2. The immunomodulating activity of chondroitin sulfate was examined by cell proliferation assay and these results suggest that it might be a immunosuppressant.     

The effect of skin surface warming during anesthesia preparation on preventing redistribution hypothermia in the early operative period of off-pump coronary artery bypass surgery.

OBJECTIVE: Redistribution hypothermia adversely affects hemodynamics and postoperative recovery in patients undergoing cardiac surgery. In off-pump coronary bypass surgery (OPCAB), maintaining the temperature is important because warming by cardiopulmonary bypass is omitted. Pre-warming studies reported earlier showing pre-warming as an effective means of preventing redistribution hypothermia was time consuming since it required at least 1-2h to pre-warm the patients before the surgery. Because pre-warming for such a long time is impractical in clinical practice, this study evaluated the efficacy of active warming during the preanesthetic period for the prevention of redistribution hypothermia in the early operative period of OPCAB. METHODS: After gaining the approval of Institutional Review Board and informed consent from the patients, 40 patients undergoing OPCAB were divided into control and pre-warming groups. The patients in control group (n=20) were managed with warm mattresses and cotton blankets, whereas patients in pre-warming group (n=20) were actively warmed with a forced-air warming device before the induction of anesthesia. Hemodynamic variables and temperature were recorded before anesthesia (Tpre) and at 30 min intervals after anesthesia for 90 min (T30, T60, and T90). RESULTS: Active warming duration was 49.7+/-9.9 min. There were no statistically significant differences in skin temperature, core temperature and hemodynamic variables between the two groups at preinduction period except for mean arterial pressure and central venous pressure. The core temperature at T30, T60, and T90 was statistically higher in pre-warming group than that in control group. Core temperature of six (30%) and seven patients (35%) in control group was reduced below 35 degrees C at T60 and T90, respectively, whereas core temperature of only one patient (5%) in pre-warming group was reduced below 35 degrees C at T90 (P=0.02). CONCLUSIONS: Active warming using forced air blanket before the induction of anesthesia reduced the incidence and degree of redistribution hypothermia in patients undergoing OPCAB. It is a simple method with reasonable cost, which does not delay the induction of anesthesia nor the surgery.     

Acute coronary syndromes

The first 150 words of the full text of this article appear below. Key points Coronary artery disease accounts for >30% ofdeaths in Western society. The diagnosis of myocardial infarctionshould be qualified by size, causation and time from occurrence. Mortalityis reduced by immediate or ‘primary’ percutaneouscoronary intervention or thrombolysis within the first 24 hof onset of ST-segment elevation myocardial infarction. Strategiesto reduce platelet activation (glycoprotein IIb/IIIa receptorantagonists, or clopidogrel) are now recommended in the treatmentof high-risk non-ST-segment myocardial infarction/unstable angina. Elevatedserum troponins may be the result of non-ischaemic myocardialdamage, especially in critical illness.