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Biodiversity and emerging diseases.

First we remind general considerations concerning biodiversity on earth and particularly the loss of genetic biodiversity that seems irreversible whether its origin is directly or indirectly linked to human activities. Urgent and considerable efforts must be made from now on to cataloge, understand, preserve, and enhance the value of biodiversity while ensuring food safety and human and animal health. Ambitious integrated and multifield research programs must be implemented in order to understand the causes and anticipate the consequences of loss of biodiversity. Such losses are a serious threat to sustainable development and to the quality of life of future generations. They have an influence on the natural balance of global biodiversity in particularly in reducing the capability of species to adapt rapidly by genetic mutations to survive in modified ecosystems. Usually, the natural immune systems of mammals (both human and animal), are highly polymorphic and able to adapt rapidly to new situations. We more specifically discuss the fact that if the genetic diversity of the affected populations is low the invading microorganisms, will suddenly expand and create epidemic outbreaks with risks of pandemic. So biodiversity appears to function as an important barrier (buffer), especially against disease-causing organisms, which can function in different ways. Finally, we discuss the importance of preserving biodiversity mainly in the wildlife ecosystems as an integrated and sustainable approach among others in order to prevent and control the emergence or reemergence of diseases in animals and humans (zoonosis). Although plants are also part of this paradigm, they fall outside our field of study.

Adaptation, Physiological↗

Changes in the use and management of forests for abating carbon emissions: issues and challenges under the Kyoto Protocol.

The global carbon cycle is significantly influenced by changes in the use and management of forests and agriculture. Humans have the potential through changes in land use and management to alter the magnitude of forest-carbon stocks and the direction of forest-carbon fluxes. However, controversy over the use of biological means to absorb or reduce emissions of CO(2) (often referred to as carbon 'sinks') has arisen in the context of the Kyoto Protocol. The controversy is based primarily on two arguments: sinks may allow developed nations to delay or avoid actions to reduce fossil fuel emissions, and the technical and operational difficulties are too threatening to the successful implementation of land use and forestry projects for providing carbon offsets. Here we discuss the importance of including carbon sinks in efforts to address global warming and the consequent additional social, environmental and economic benefits to host countries. Activities in tropical forest lands provide the lowest cost methods both of reducing emissions and reducing atmospheric concentrations of greenhouse gases. We conclude that the various objections raised as to the inclusion of carbon sinks to ameliorate climate change can be addressed by existing techniques and technology. Carbon sinks provide a practical available method of achieving meaningful reductions in atmospheric concentrations of carbon dioxide while at the same time contribute to national sustainable development goals.

Air Pollutants↗

Calcium-induced ventricular contraction during cardioplegic arrest.

Cardiac arrest induced by hyperkalemic perfusion is generally considered to represent a state of complete electromechanical arrest. However, high-energy phosphate concentrations and ventricular function decrease with increasing cardioplegic calcium concentrations, possibly because of elevated resting muscle tone produced by calcium influx. We examined isolated rat hearts containing an isovolumic intraventricular balloon for the presence of contractile activity during the administration at 10 degrees C of a cardioplegic solution containing potassium, 20 mEq/L. Significant left ventricular pressure was developed (35.6% +/- 4.3% of prearrest systolic pressure) during administration of a solution containing a calcium concentration of 1.0 mmol/L and far less (9.7% +/- 1.6% of prearrest systolic pressure) with a calcium-free cardioplegic solution. The muscle contraction diminished with repeated doses, was increased by increasing cardioplegic calcium content, and was inhibited by magnesium. Adenosine triphosphate and creatine phosphate concentrations were 9.0 +/- 1.4 and 7.0 +/- 0.9 nmol/mg dry weight immediately after infusion of 15 ml of a hypoxic cardioplegic solution containing calcium, versus 13.3 +/- 1.3 (p less than 0.02) and 31.9 +/- 3.5 nmol/mg dry weight (p less than 0.0001) after a hypoxic acalcemic solution was given. When repeated doses of a hypoxic cardioplegic solution containing calcium in a concentration of 1.0 mmol/L were given at 15 minute intervals at 10 degrees C, ischemic contracture (a sustained development of ventricular pressure, mean 51% +/- 4% of prearrest systolic pressure) resulted within 1 hour. Coronary vascular resistance was increased during the muscle contractions induced by calcium-containing solutions, markedly so during contracture. Calcium-related mechanical activity was also observed during hypothermic cardioplegic arrest in five of six isolated isovolumic canine hearts. We conclude that hearts remain potentially active mechanically during cold hyperkalemic arrest and undergo energetically wasteful contraction when stimulated with calcium-containing hyperkalemic cardioplegic solutions.

Adenine Nucleotides↗

On evolution and perspectives of bio-watersaving.

As shortage in water resources is a fact, bio-watersaving becomes one hot topic at present. The concept of bio-watersaving has been developed from agronomic watersaving to physiological watersaving then to gene watersaving. The definition of bio-watersaving is yielding more agricultural productions under the same water condition by exploiting the physiological and genetic potential of organisms themselves. There are two aspects in bio-watersaving: one is managing crop system and watersaving irrigation according to the drought characteristics and physiological water need of plants; the second is breeding new varieties with good drought resistance and high water use efficiency (WUE) and high yield and good quality traits, through exploiting new drought resistance genes and high WUE genes with the aid of biotechnology. Gene watersaving is the base for physiological watersaving, so gene watersaving has the biggest potential to be exploited in future, and will play an important role in high use efficiency of water and soil resources, and agricultural sustainable development in China and the globe.

Adaptation, Biological↗

Intermediate stage complex regional pain syndrome type 1 is unrelated to proinflammatory cytokines.

The aim of this paper is to determine the involvement of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in intermediate CRPS 1 as locally formed mediators of inflammation. In this study, 25 patients with proven CRPS 1 (Bruehl criteria) were included. All patients participated in one of our earlier studies during the acute stage of their disease. After the disease developed into an intermediate stage, both the disease activity and the profile of inflammatory mediators were reevaluated. Disease activity and impairment were determined by means of a visual analogue scale, the McGill Pain Questionnaire, the difference in volume and temperature between the involved and uninvolved extremities, and the reduction in active range of motion of the involved extremity. Suction blisters were made on the involved and uninvolved extremities for measurement of IL-6 and TNF-alpha. A significant improvement in signs and symptoms of impairment was found. However, the levels of IL-6 and TNF-alpha in blister fluid in the involved extremity versus uninvolved extremity were still significantly raised. Although signs and symptoms are significantly improved, proinflammatory cytokines are still increased in CRPS 1 affected extremities during the intermediate stage of the disease. This indicates that the initiation and sustained development of the disease are only partially affected by proinflammatory cytokines. Follow-up in the chronic stage is necessary to draw more definite conclusions about the existence of a supposed relation between clinical signs and symptoms and the level of proinflammatory cytokines.

Complex Regional Pain Syndromes↗

Radiofrequency catheter ablation of the atria eliminates pacing-induced sustained atrial fibrillation and reduces connexin 43 in dogs.

BACKGROUND: We assessed the effects of radiofrequency catheter ablation (RFCA) of the atrial epicardium on pacing-induced sustained atrial fibrillation (AF) and the expression and distribution of the intercellular gap junction protein connexin 43 (Cx43) in dogs. METHODS AND RESULTS: In 12 mongrel dogs, after creation of complete AV block and implantation of a ventricular inhibited pacemaker, a high-rate pulse generator (20 to 30 Hz to induce AF) was implanted in the neck, connected to a right atrial endocardial pacing lead, and used to pace the atrium for 10 to 14 weeks. In group 1 (n=9 dogs), corrected sinus node recovery time (CSNRT), P-wave duration, 24-hour Holter ECG, maximal heart rate (MHR) in response to isoproterenol, and intrinsic heart rate (IHR) after atropine (0.04 mg/kg) and propranolol were measured before and after atrial pacing and RFCA. Group 2 dogs were used to assess the effect of chronic AF alone on Cx43 expression and distribution. All group 1 dogs developed sustained (>24 hours) AF. Right-sided RFCA of the atria eliminated the sustained AF in 5 dogs, but both right and left atrial RFCA was required to abolish sustained AF in the other 4 dogs. After RFCA restored sinus rhythm, CSNRT and P-wave duration were prolonged and MHR and IHR were decreased. Chronic rapid atrial pacing (group 2) increased the expression of Cx43, which was absent in ablated areas and markedly depressed in viable atrial myocytes near the ablation zones (group 1). CONCLUSIONS: Rapid atrial pacing for long time periods induced sustained AF that can be eliminated by linear right and left atrial lesions created with RFCA, with preservation of sinus rhythm and atrial contractile function. Chronic AF increased the expression and distribution of gap junction protein Cx43, which became reduced in ablated and nearby nonablated areas.

Animals↗

Chronic anemia in pregnant ewes: maternal and fetal effects.

To examine maternal and fetal responses to a sustained reduction in maternal hematocrit during days 110-138 of ovine gestation, 22 ewes and their singleton fetuses were instrumented. By repetitive exchange transfusions, the hematocrit in 12 ewes was decreased from 28.1 +/- 0.8 (baseline, day 110) to 14.0 +/- 0.7% (day 117) and maintained at that level. Anemic ewes demonstrated a transient increase in heart rate from 99 +/- 4 to 116 +/- 4 beats/min and a sustained increase in cardiac output from 117 +/- 8 to 153 +/- 11 ml.min-1.kg-1 compared with control animals. Uterine blood flow steadily increased in control animals from 868 +/- 100 (day 110) to 1,410 +/- 177 ml/min (day 138) but failed to increase in the anemic ewes. Uterine oxygen delivery fell from 83 +/- 10 to 39 +/- 4 ml/min with production of anemia and remained low in the anemic ewes. Arterial PO2 and oxygen content in the fetuses of anemic ewes fell transiently below control values (19.9 +/- 0.8 vs. 23.4 +/- 1.0 mmHg and 5.3 +/- 0.3 vs. 6.8 +/- 0.4 ml/dl, respectively) but did not persist. Fetal weights at 138 days gestation were lower in the anemic group (2,596 +/- 329 vs. 4,313 +/- 132 g). We conclude that chronic maternal anemia results in a decreased uterine blood flow as well as decreased uterine oxygen delivery. The fetus responds with decreased growth but does not develop sustained hypoxia or acidosis.

Anemia↗

[Plant diversity of different replaced communities after Eupatorium adenophorum removal].

Plant diversity of different replaced communities after Eupatorium adenophorum removal. WANG In this paper, an investigation on the structure, species composition and plant diversity of replaced communities after the removal of invasive E. adenophorum at the beginning of 1980s was made in the Shuangbo County of Yunnan Province, with local aged Pinus yunnanensis and unmanaged E. adenophorum forests as the reference. The results showed that in replaced communities, the richness, Shannon-Wiener, Simpson, and Pielou evenness indices values of woody species were 25 to approximately 28, 1.06 to approximately 2.34, 0.36 to approximately 0.86 and 0.32 to approximately 0.73, and those of herb species were 6 to approximately 8, 1.51 to approximately 1.97, 0.74 to approximately 0.84 and 0.84 to approximately 0.90, respectively. In unmanaged E. adenophorum community, the corresponding indices values of woody species were 3, 0.14, 0.10 and 0.13, and those of herb species were 3, 0.09, 0.03 and 0.08, respectively, being much lower than those of the replaced communities. The replaced communities dominated by fast-growing tree species in E. adenophorum forest developed through a 20 years rehabilitation period, under which, there was a clear understory layer dominated by native species. The density and growth rate of E. adenophorum was inhibited in the replaced communities. In comparison with the E. adenophorum community, the plant diversity of replaced communities was greatly increased. Among the replaced communities, P. yunnanensis + Schima wallichii + Eucalyptus globules community had the greatest plant diversity, but the replaced communities had lower plant diversity than the aged P. yunnanensis, with 42, 2.88, 0.92 and 0.77 for woody species, and 8, 2.08, 0.86 and 0.90 for herb species, respectively. It was suggested that more attention should be paid to conserve the rehabilitated communities, especially the P. yunnanensis plantation built on the degraded lands invaded by E. adenophorum. In addition, the introduction of local broad-leaved species and some shade-loving herb plants into these plantations and its follow-up management were also important for the sustainable development of the revegetation.

Ageratina↗

Evaluation of a euglycaemic clamp procedure as a diagnostic test in insulinoma patients.

In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypoglycaemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (less than or equal to 2.3 mmol l-1) within 2-44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR-insulin) concentrations. IR-proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady-state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4-5.0 mmol l-1 was significantly (P less than or equal to 0.001) higher in insulinoma patients (2.5 +/- 0.6 mg kg-1 min-1) than in pancreas resected patients (0.6 +/- 0.2 mg kg-1 min-1), or in control subjects (0.5 +/- 0.1 mg kg-1 min-1). Due to a considerable degree of overlap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR-insulin values (r = 0.024, P = 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR-insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of 'amended' insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR-C-peptide plasma concentrations) by 52-88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de-differentiated tumours. In contrast to this significant (P = 0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal beta-granules, and does not distinguish adenomas from carcinomas.

Adenoma, Islet Cell↗

Forecasting loss of ecosystem service value using a BP network: a case study of the impact of the South-to-north Water Transfer Project on the ecological environmental in Xiangfan, Hubei Province, China.

OBJECTIVE: To recognize and assess the impact of the South-to-north Water Transfer Project (SNWTP) on the ecological environment of Xiangfan, Hubei Province, situated in the water-out area, and develop sound scientific countermeasures. METHODS: A three-layer BP network was built to simulate topology and process of the eco-economy system of Xiangfan. Historical data of ecological environmental factors and socio-economic factors as inputs, and corresponding historical data of ecosystem service value (ESV) and GDP as target outputs, were presented to train and test the network. When predicted input data after 2001 were presented to trained network as generalization sets, ESVs and GDPs of 2002, 2003, 2004... till 2050 were simulated as output in succession. RESULTS: Up to 2050, the area would have suffered an accumulative total ESV loss of RMB104.9 billion, which accounted for 37.36% of the present ESV. The coinstantaneous GDP would change asynchronously with ESV, it would go through an up-to-down process and finally lose RMB89.3 billion, which accounted for 18.71% of 2001. CONCLUSIONS: The simulation indicates that ESV loss means damage to the capability of socio-economic sustainable development, and suggests that artificial neural networks (ANNs) provide a feasible and effective method and have an important potential in ESV modeling.

China↗

An environmental analysis for comparing waste management options and strategies.

The debate on different waste management practices has become an issue of utmost importance as human activities have overloaded the assimilative capacity of the biosphere. Recent Italian law on solid waste management recommends an increase in material recycling and energy recovery, and only foresees landfill disposal for inert materials and residues from recovery and recycling. A correct waste management policy should be based on the principles of sustainable development, according to which our refuse is not simply regarded as something to eliminate but rather as a potential resource. This requires the creation of an integrated waste management plan that makes full use of all available technologies. In this context, eMergy analysis is applied to evaluate three different forms of waste treatment and construct an approach capable of assessing the whole strategy of waste management. The evaluation included how much investment is needed for each type of waste management and how much "utility" is extracted from wastes, through the use of two indicators: Environmental yield ratio (EYR) and Net eMergy. Our results show that landfill is the worst system in terms of eMergy costs and eMergy benefits. Composting is the most efficient system in recovering eMergy (highest EYR) from municipal solid waste (MSW) while incineration is capable of saving the greatest quantity of eMergy per gram of MSW (highest net eMergy). This analysis has made it possible to assess the sustainability and the efficiency of individual options but could also be used to assess a greater environmental strategy for waste management, considering a system that might include landfills, incineration, composting, etc.

Conservation of Energy Resources↗

The zootechnical applications of biotechnology in animal reproduction: current methods and perspectives.

The development of the four generations of Reproductive Biotechnology, particularly in cattle and since the last world war, represents one of the best examples of the success story of technology transfer. This review will only refer to the first three generations and will not deal with nuclear transfer nor transgenesis. Based on sound so-called "finalised" research, Artificial Insemination first, then in vivo collected embryo transfer and later in vitro fertilised embryo transfer have been implemented worldwide. Each of these Biotechnologies has many advantages and limitations. In addition to the specificity of each of them, one major point is that farmers and breeders may choose either collectively or individually, the best technology to be used in order to achieve the goals they have set for their industry. It is noteworthy that these technologies have been able to match with the economics demands over the last decades and yet are in a very good capacity to respond to the contemporary demand of sustainable development. In this context, there are further advantages such as potentially contributing to maintaining biodiversity or allowing preservation ex situ of genes otherwise threatened to extinction.

Animal Husbandry↗

A multicenter study of the efficacy and safety of sustained release GH in the treatment of naive pediatric patients with GH deficiency.

Treatment of naive children with GH deficiency has relied upon long-term replacement therapy with daily injections of GH. The daily schedule may be inconvenient for patients and their caregivers, possibly promoting nonadherence with the treatment regimen or premature termination of treatment. We studied a new sustained release GH formulation, administered once or twice monthly, to determine its efficacy and safety in this population. Seventy-four prepubertal patients with documented GH deficiency were randomized to receive sustained release recombinant human GH at either 1.5 mg/kg once monthly or 0.75 mg/kg twice monthly by sc injection in a 6-month open-label study. Efficacy was determined by growth data from 69 patients completing 6 months and 56 patients completing 12 months in an extension study. Growth rates were significantly increased over baseline and were similar for the two dosage groups. The mean (+/-SD) annualized growth rate (pooled data) was 8.4 +/- 2.1 cm/yr at 6 months, and the growth rate was 7.8 +/- 1.8 at 12 months compared with 4.5 +/- 2.3 at baseline. Standardized height, bone age, and predicted adult height assessments demonstrated catch-up growth without excessive skeletal maturation. Injection site-related events (including pain, erythema, and nodules) were the most commonly reported adverse events; no serious adverse events related to treatment were reported. Laboratory studies documented no accumulation of trough GH or IGF-I levels during treatment, nor did glucose intolerance or persistent hyperinsulinism develop. Sustained release recombinant human GH is safe and effective for long-term GH replacement in children with GH deficiency. Patients achieved similar growth velocities when sustained release GH was given once or twice monthly. The enhanced convenience of this dosage form may result in greater long-term adherence to the treatment regimen.

Antibodies↗

Incidence and significance of ventricular tachycardia and fibrillation in the absence of hypotension or heart failure in acute myocardial infarction treated with recombinant tissue-type plasminogen activator: results from the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial.

OBJECTIVES: The purpose of this study was to determine the incidence of ventricular tachycardia and fibrillation without hypotension or heart failure after treatment with recombinant tissue-type plasminogen activator (rt-PA), anatomic correlates of their development, the effect of immediate intravenous metoprolol on their occurrence and the outcome of patients with these arrhythmias. BACKGROUND: Malignant arrhythmias after thrombolytic therapy have been reported to occur as a result of coronary reperfusion, which is associated with reduced mortality in patients receiving thrombolytic therapy. METHODS: We analyzed data from 2,546 patients in the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial without congestive heart failure or hypotension during the 1st 24 h after study entry. Forty-nine patients (1.9%) developed sustained ventricular tachycardia or ventricular fibrillation within 24 h of study entry (group 1), and 2,497 patients (98.1%) did not (group 2). RESULTS: Baseline characteristics and admission laboratory values were similar in the two groups. In patients undergoing protocol angiography 18 to 48 h after rt-PA, the infarct-related artery was patient in a greater percent of group 2 patients (87% [1,015 of 1,169]) than group 1 patients (68% [15 of 22], p = 0.01), although angiography was performed less frequently in group 1 than in group 2. More group 1 than group 2 patients died within 21 days (20.4%) (1.6%, p < 0.001). For patients surviving to 21 days, there was no difference in mortality between patients in the two groups in the following year. CONCLUSIONS: Ventricular tachycardia and fibrillation are not markers for reperfusion after thrombolytic therapy. These arrhythmias are associated with occlusion, not patency, of the infarct-related artery. Early mortality is increased in patients who develop ventricular tachycardia and fibrillation, even in the absence of congestive heart failure and hypotension.

Female↗

Optimization of solid fermentation of cellulase from Trichoderma koningii.

To exploit peashrub resources in Ordos as fodders, it is very crucial to realize industrial production of cheap cellulase of high activity by optimizing culture technology, especially culture substrate. In this study, a new prescription experiment based on uniform design ideal was invented and successfully applied in the solid fermentation of Trichoderma koningii F244, which was performed with two different temperature degrees. The activities of FPA, cotton lyase, CMCase and beta-glucosidase were assayed and then mathematical models of enzymatic activities, which were figured out by Unconstraint Mathematical Programming, were developed by Multivariate Regression Program of SPSS10.0. Enzymatic activities of optimized substrate prescriptions corresponding to mathematical models were forecasted to determine an ideal substrate prescription. It is revealed that in solid fermentation, Tween80 has negative effect on cellulase production. Furthermore, the ideal prescription for cellulase complex production by Trichoderma koningii F244 was straw powder 16.9%, wheat bran 26.5%, (NH4)2SO4 9.5% and water 47.1%, whose corresponding cellulase activity was expected to be at the same high level with that of Trichoderma reesei Q9414 on its own recommended substrate. Especially, goats mainly fed on peashrub tissues mixed with cellulase complex of this prescription and culture technology, got an incremental ratio of 0.3 kg/d, which brought a very promising feeding prospect for local peashrub resource. By populization of this cellulase complex, it can integrate living standard, economic construction of local residents into vegetational restoration tightly and thus this paper will be very meaningful to be use for reference for western China like Ordos to realize its sustainable development of economy, society and environment.

Agriculture↗

[Environmental quality: wellfare, confort and health].

Different ways of interpreting environmental conditions have led to the development of concepts such as the sick building, indoor air quality or indoor environment quality, for understanding the complexity of the pollutants in enclosed environments and the implications thereof on the health. The "Indoor Environment Quality" proposal is an advancement, operative and conceptual, surpassing amply prior ones, given that it orients the actions toward healthy environments without limiting the idea of pollution to the air alone. The aim is identifying the competence to preventing hazards related to exposure to pollutants within the confines of indoor environments and know the legislative framework useful for taking the actions. Optimum conditions within indoor environments must redound in health, well-being and comfort with regard to both working life as well as the environments in which everyday activities outside of work, extracurricular, leisure-time and entertainment activities are carried out. Today's society is demanding safe, clean, well-climatized places, for this is necessary to integrate the inhabitant's perceptions and demands and achieve an optimum balance among social standards, energy use and sustainable development. Legislation is being further expanded upon in the direction of occupational health and safety and the regulation of chemical substances. Environmental Health carries out prevention and control tasks, takes part in the enforcement of international pollution and waste reduction agreements and promotes measures for carrying out the European Environment and Health Strategy. It is considered useful the elaboration of protocols for the evaluation and administration gives the risks associated to the interior pollutants.

Air Pollution, Indoor↗

Cellular mechanisms of atrial contractile dysfunction caused by sustained atrial tachycardia.

BACKGROUND: Transient atrial contractile dysfunction ("atrial stunning") follows conversion of atrial fibrillation (AF) to sinus rhythm and has significant clinical implications; however, the underlying mechanisms are poorly understood. We investigated the hypothesis that rapid atrial activation (as during AF) impairs cellular contractility and affects cellular Ca2+ handling. METHODS AND RESULTS: Edge detection and indo 1 fluorescence techniques were used to measure unloaded cell shortening and intracellular Ca2+ transients in atrial myocytes from control (Ctl) dogs and dogs subjected to atrial pacing at 400 bpm for 7 (P7) or 42 (P42) days. Atrial tachycardia reduced fractional cell shortening (0.1 Hz) from 7.3+/-0.4% (Ctl) to 4.3+/-0.3% and 2.0+/-0.3% in P7 and P42 dogs, respectively (P<0.01 for each). Resting [Ca2+]i was not altered in paced dogs, but the systolic Ca2+ transient was significantly reduced. Furthermore, cells from paced dogs showed slowed relaxation and use-dependent decreases of Ca2+ transients and cell shortening compared with cells from Ctl dogs. To determine whether changes in Ca2+ transients account fully for alterations in contractility, we varied [Ca2+]o to evaluate the relation between Ca2+ transients and cell shortening. Reductions in Ca2+ transients in Ctl cells reduced shortening to the level of paced cells; however, when Ca2+ transients in P42 cells were elevated to the range of Ctl cells, a significant reduction in cell shortening remained. Similar results were obtained in dogs that maintained 1:1 capture throughout the monitoring period and dogs that developed sustained AF over the course of the study. CONCLUSIONS: Sustained atrial tachycardia causes important reductions in cellular contractility, in part by impairing cellular Ca2+ handling and decreasing systolic Ca2+ transients. These results provide direct evidence for the concept that AF induces atrial contractile dysfunction by causing a tachycardia-induced atrial cardiomyopathy.

Animals↗

Instant and sustained-release verapamil in the treatment of essential hypertension.

In a series of controlled studies for periods of 4 to 6 weeks comprising 103 patients altogether, and in 1 long-term trial for 1 year, various dosages of instant and sustained-release verapamil were administered in the treatment of mild and moderate essential hypertension. One of these trials was a double-blind comparison with nifedipine, in which the 2 calcium antagonists had an equally good effect on blood pressure. A significant blood pressure reduction was achieved with verapamil both at rest and during isometric work in most patients. About 10% of the patients were nonresponders. Pharmacokinetic studies demonstrated great interindividual variations in plasma concentrations of verapamil and its active metabolite norverapamil. Except for 1 study, no significant correlation was found between drug concentration and blood pressure reduction. All formulations of verapamil were well tolerated by the patients, and adverse effects were generally mild and often transient. No negative metabolic effects were observed during long-term treatment; serum lipids, in particular, were unaffected. PQ intervals on the electrocardiogram were significantly but moderately prolonged. QRS and QT intervals were unchanged. No increase in body weight occurred. It is concluded that verapamil is an efficacious, safe drug and a first-line treatment alternative in mild and moderate essential hypertension. The recently developed sustained formulation of the drug renders a simple dosage regimen possible.

Adult↗