Mechanical restitution curves: a possible load independent assessment of contractile function.

OBJECTIVE: The time constant of mechanical restitution (T((MRC))), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure, and might have a potential as an index of contractile function. However, in vivo studies of the effect on T((MRC)) of changing loading conditions in the normal and failing heart have not been reported. Consequently, in this study, we tested the hypothesis that the increase in T((MRC)) in vivo is independent of preload and afterload. METHODS: Left ventricular pressure-volume loops were assessed at baseline in eight open chest pigs using the combined pressure-volume conductance catheter technique during right atrial pacing at 120b/min. Mechanical restitution curves (MRC) were constructed during four different loading conditions in all eight animals: uninfluenced load, reduced preload (balloon catheter in v. cava inferior), increased afterload (balloon catheter in descending aorta), and increased preload combined with reduced afterload (aortocaval shunting). Acute LV failure was then induced by microembolization through the left main coronary artery, and the experimental protocol was repeated. Contractile response was defined as the maximal first derivative of pressure (dP/dt(max)), and T((MRC)) was calculated using a least square approximation algorithm. RESULTS: Hemodynamic data 30min after microembolization showed decreased mean arterial pressure (98+/-14-67+/-10mmHg, (mean+/-SD) P<0.0001) and dP/dt(max) (1482+/-193-1001+/-125mmHg/s, P=0.001). Stroke volume decreased from 30+/-5 to 20+/-5ml (P<0.0001) compared to baseline, and preload recruitable stroke work decreased from 52+/-7 to 31+/-10mmHg (P=0.002). T((MRC)) increased in all eight animals after induction of LV failure at all loading conditions. There was no difference between the different loading conditions at baseline, nor at LV heart failure, but T((MRC)) increased significantly after the induction of heart failure (ANOVA, two ways). CONCLUSIONS: We have shown that the left ventricular T((MRC)) increases after developed heart failure. The increase in T((MRC)) was independent on loading conditions and thus have a potential for a contractility index.     

Wear of the Christiansen hip prosthesis

The wear was examined in 39 Christiansen total hip prostheses, which were removed because of mechanical loosening after being used 5 (3-11) years. In the polyacetal acetabular cups, the head had made an eccentric defect, the mean volume of which was 680 (180-3310) mm³. The mean penetration of the head into the wall of the cup was 0.8 (0.1-3.2) mm. In two additional cups the head had penetrated right through the wall of the cup. In three prostheses the polyacetal sleeve of the trunnion was so worn that the head bore directly on the stem. There was a positive correlation between wear and the time the prostheses had been used before symptoms of loosening presented.     

Occupational exposure of deck crews to carcinogenic agents on crude oil tankers

Occupational exposure to carcinogenic agents on the decks on six Norwegian crude oil tankers was examined in five harbors. The purpose of the study was to evaluate the need for improving the working environment on deck on these tankers. Technical arrangments and the work itself on the deck were observed during loading or unloading. Occupational monitoring was performed by active sampling of benzene, polyaromatic hydrocarbons, and some aldehydes. The crew answered a questionnaire concerning their work, use of protective equipment, and occurrence of acute symptoms. The levels of air-borne carcinogenic agents were low, probably due to closed loading systems on all tankers. However, the seamen reported discomfort during the work that may be related to other chemical agents in the cargo. The seamen were frequently painting with lead chromate paint without using personal protective equipment. This type of chemical exposure should be evaluated.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Impaired early bone formation in periodontal fenestration defects in dogs following application of insulin-like growth factor (II). Basic fibroblast growth factor and transforming growth factor beta 1

Abstract. Effects of a topically applied growth factor combination on fibroblast migration, collagen fiber formation and bone regeneration were studied in standardized periodontal defects in 4 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and into the dentin of maxillary and mandibular teeth. Collagen sponges, impregnated with 200 ng insulin-like growth factor II, 20 ng basic fibroblast growth factor and 6 ng transforming growth factor beta 1 were fitted to defects randomly in right or left quadrants and the flaps repositioned and sutured. Contralateral control defects received the collagen with vehicle only. Experimental procedures were staggered to allow observations of healing 3, 7, 10, and 14 days after surgery. Histometric analysis showed no differences in fibroblast and collagen density between control and growth factor defects. Bone regeneration was significantly greater in control than in growth factor defects 10 and 14 days after surgery. The rate of healing generally appeared more affected by intra-dog variations or procedural variations than by the growth factor combination.     

Bronchial response to breathing dry gas at 3.7 MPa ambient pressure

In diving, pulmonary mechanical function is limited by the increased density of the gas breathed. Breathing cold and dry gas may cause an additional increase in airways resistance. We have measured forced vital capacity, forced expired volume in 1 s (FEV₁) and forced midexpiratory flow rate (FEF_25%–75%) before and after breathing dry or humid gas at 29–32°C during a standardized exercise intensity on a cycle ergometer at an ambient pressure of 3.7 MPa. The atmosphere was a helium and oxygen mixture with a density of 6.8 kg · m^–3. Six professional saturation divers aged 26–37 years participated in the study. There were no significant differences in convective respiratory heat loss between the exposures. The mean evaporative heat loss was 67 W (range 59–89) breathing dry gas and 37 W (range 32–43) breathing humid gas, corresponding to water losses of 1.7 g · min^–1 (range 1.5–2.2) and 0.9 g · min^–1 (range 0.8–1.1), respectively. There was a significant reduction in FEV₁ of 4.6 (SD 3.6)% (P<0.05), and in FEF_25%–75% of 5.8 (SD 4.7)% (P<0.05) after breathing dry gas. There were no changes after breathing humid gas. By warming and humidifying the gas breathed in deep saturation diving bronchoconstriction may be prevented.     

Cardiology

This article describes recent developments in cardiology and cardiovascular disease that are likely to be relevant to primary healthcare professionals and their patients. The following subject areas are covered: Primary prevention: recent developments in pharmaco-logical interventions, drug interactions, and drugs that are likely to cause harm; cardiovascular risk estimation and shared decision making with patients; and new developments in 24-hour ambulatory blood pressure monitoring. Secondary prevention: new models of care, including nurse-led care for the provision of hypertension and secondary prevention clinics; new drugs for the treatment of angina and myocardial infarction; ambulatory electrocardiography for the diagnosis of arrhythmias in primary care; and new developments in the treatment of atrial fibrillation - direct thrombin inhibitors and implantable devices. Tertiary prevention: recent developments in cardiac rehabilitation; recent evidence concerning revascularisation procedures and appropriateness criteria for referral; and implantable defibrillators.     

Effects of exposure to an estrous female on forebrain monoaminergic neurotransmission in the non-copulating male rat

Regional changes in the rate of brain monoamine synthesis were monitored in male rats exposed to, but prevented from physical contact with, an estrous or an ovariectomized female. The in vivo rate of tyrosine and tryptophan hydroxylase activities were estimated by measuring the accumulation of DOPA and 5-HTP following inhibition of cerebral aromatic l-amino acid decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015) treatment (100 mg/kg i.p.) 5 min upon NSD-1015 treatment, the males were exposed to an intact estrous female or an ovariectomized female for 20 min before decapitation and brain dissections. Exposure to an estrous female produced an increased rate of tyrosine and tryptophan hydroxylase activity in the medial prefrontal cortex, the dorso-lateral neostriatum and in the ventral neostriatum, in comparison with home-cage controls. By the same comparison, exposure to an ovariectomized female resulted in an increased rate of tyrosine hydroxylase activity in the medial prefrontal cortex, byt not in the neostriatal areas, whereas tryptophan hydroxylase activity was unaffected. Finally, exposure to the empty test cage, with no stimulus females present, did not produce any statistically significant changes in the rate of tyrosine or tryptophan hydroxylase activity in any of the brain areas sampled. Taken together with recent findings from this laboratory, the present results demonstrate that the level of sexual motivation brought about by the olfactory, auditory and/or visual stimulation of a receptive female is associated with an increased demand on catecholamine and 5-hydroxytryptamine synthesis in the limbic forebrain of the male rat. The finding that the presence of an unestrous female produced an enhanced demand on tyrosine hydroxylase activity in the medial prefrontal neocortex demonstrates that the sexual incentive provided by the estrous female may not be the only factor responsible for all the effects observed in the present study. In fact, there is a distinct possibility that the intense challenge produced by sexually significant stimuli is but an endpoint, and that the changes found in forebrain monoamine synthesis is a reflection of an environmental challenge not necessarily specifically linked to the sexual behavior.     

Infectious salmon anemia virus (ISAV) genomic segment 3 encodes the viral nucleoprotein (NP), an RNA-binding protein with two monopartite nuclear localization signals (NLS)

Infectious salmon anemia virus (ISAV) is the type species of the genus Isavirus belonging to the Orthomyxoviridae, and causes serious disease in Atlantic salmon (Salmo salar). This study presents the expression and functional analysis of the ISAV genome segment 3, and provides further evidence that it encodes the viral nucleoprotein (NP). The encoded protein was expressed in a baculovirus system, and Western blot analysis showed that it corresponds to the 66-71 kDa structural protein previously found in purified ISAV preparations. RNA-binding activity was established by the interaction of viral and recombinant NP with single-stranded RNA transcribed in vitro. Immunofluorescence studies of infected cells showed the ISAV NP to be an early protein. It locates to the nucleus of infected cells before it is transported to the cytoplasm prior to virus assembly. A similar localization pattern was observed in cells transfected with the NP gene, confirming that the encoded protein has an intrinsic ability to be imported into the nucleus. Two monopartite nuclear localization signals (NLS) at amino acids (230)RPKR(233) and (473)KPKK(476) were identified by computer analysis, and validated by site-directed mutagenesis. In contrast to other orthomyxovirus-NPs, that have several NLSs that function independent of each other, both NLSs had to be present for the ISAV NP protein to be transported into the nucleus, indicating that these motifs cooperate to target the protein to the nucleus.