In vivo toxicity study of quatro stimuli nanocontainers in pregnant rats: Gestation, parturition and offspring evaluation.

The aim of the present study was to investigate the impact of intravenous administration of newly fabricated nanocontainers (NCs) on the last third of pregnancy in rats. Fifteen pregnant 3-month-old Wistar rats were separated into 3 groups. On the 15th and 17th day of pregnancy all animals received an intravenous administration of 1 ml of 15 mg of NCs (Group A), 1 ml of 5 mg NCs (Group B) while Control group received 1 ml of 0.9% NaCl. On the 14th and 17th of pregnancy ultrasonography was performed and the parameters evaluated were the width of placenta, the length and width of the embryonic sac, the foetus length and the heart rate. On parturition the number of pups per dam was evaluated. Half of the pups were euthanised the day after parturition and their liver and kidney was histologically evaluated and for the rest of the pups the body growth curve was evaluated until the age of 14 week. At the end of the 14th week the remaining pups were euthanised and their liver and kidney was histologically evaluated. At weaning the dams were euthanised and their liver and kidney was histologically evaluated. Ultrasonography: Baseline measurements of the width of placenta, the length and width of embryonic sac, the foetus length and the heart rate on the 14th day of pregnancy, revealed no statistical significant differences between groups. Comparison of the same values on the 17th day of pregnancy after 2 intravenous administrations of NCs showed no statistical significant effect on the respective parameters. The administration of NCs had no impact on the mean number of pups per dam. Additionally, no impact of the NCs on the body weights of the pups was observed on the 1st day after parturition. Moreover, comparisons between groups, for both sexes showed no difference on growth rate. During the histological evaluation no inflammatory, degenerative or neoplastic lesions were observed as far as the newborn, adult offspring and dams were concerned. According to our results no toxic impact of the low and high doses of the NCs was observed on the parameters selected to be evaluated.

Effects of early amiodarone administration during and immediately after cardiopulmonary resuscitation in a swine model.

BACKGROUND: Aim of this experimental study was to compare haemodynamic effects and outcome with early administration of amiodarone and adrenaline vs. adrenaline alone in pigs with prolonged ventricular fibrillation (VF). METHODS: After 8 min of untreated VF arrest, bolus doses were administered of adrenaline (0.02 mg/kg) and either amiodarone (5 mg/kg) or saline (n = 8 per group) after randomisation. Cardiopulmonary resuscitation (CPR) was commenced immediately after drug administration, and defibrillation was attempted 2 min later. CPR was resumed for another 2 min after each defibrillation attempt, and the same dose of adrenaline was given every 4th minute during CPR. Haemodynamic monitoring and mechanical ventilation continued for 6 h after return of spontaneous circulation (ROSC), and the pigs were euthanised at 48 h. Researchers were blinded for drug groups throughout the study. RESULTS: There was no difference in rates of ROSC and 48-h survival with amiodarone vs. saline (5/8 vs. 7/8 and 0/8 vs. 3/8, respectively). Diastolic aortic pressure and coronary perfusion pressure were significantly lower with amiodarone during CPR and 1 min after ROSC (P < 0.05). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone (P < 0.01). The incidence of post-resuscitation tachyarrhythmias tended to be higher in the saline group (P = 0.081). CONCLUSION: Early administration of amiodarone did not improve ROSC or 48-h survival rates, and was associated with worse haemodynamics in this swine model of cardiac arrest.

The use of mice and rats as animal models for cardiopulmonary resuscitation research.

Cardiopulmonary resuscitation (CPR) after the induction of cardiac arrest (CA) has been studied in mice and rats. The anatomical and physiological parameters of the cardiopulmonary system of these two species have been defined during experimental studies and are comparable with those of humans. Moreover, these animal models are more ethical to establish and are easier to manipulate, when compared with larger experimental animals. Accordingly, the effects of successful CPR on the function of vital organs, such as the brain, have been investigated because damage to these vital organs is of concern in CA survivors. Furthermore, the efficacy of several drugs, such as adrenaline (epinephrine), vasopressin and nitroglycerin, has been evaluated for use in CA in these small animal models. The purpose of these studies is not only to increase the rate of survival of CA victims, but also to improve their quality of life by reducing damage to their vital organs after CA and during CPR.

Cardiopulmonary arrest and resuscitation in Landrace/Large White swine: a research model.

Sudden cardiac death (SCD) is a field of continuous research. In order to answer various questions regarding SCD, several animal models have been developed. The aim of the present study is to describe our experimental model of inducing cardiac arrest in Landrace/Large White pigs, and then resuscitated according to the International Guidelines on resuscitation. Fifteen Landrace/Large White pigs were anaesthetized and intubated while spontaneously breathing. The left and right jugular veins, as well as the femoral and the carotid arteries, were surgically prepared. Induction of cardiac arrest was achieved by using an ordinary rechargeable lithium battery, through a pacemaker wire inserted into the right ventricle. The typical Advanced Life Support (ALS) protocol was followed, and in case of restoration of spontaneous circulation, the animals were further evaluated for 30 min. Seven animals were successfully resuscitated using this protocol, whereas eight failed resuscitation efforts. Successful resuscitation was contingent on the restoration of the levels of coronary perfusion pressure and PETCO(2) during chest compressions. Among the different ways of inducing cardiac arrest, the ordinary lithium battery is a simple, safe and valuable technique. Landrace/Large White pigs' baseline haemodynamics closely resemble human haemodynamics, making the breed a favourable model for resuscitation.

The reporting of clinical signs in laboratory animals: FELASA Working Group Report.

Observing and reporting clinical signs in laboratory animals is necessary for many reasons: the assessment of animal welfare, compliance with the principle of refinement (e.g. humane endpoints), regulatory compliance (e.g. reporting severity) and, importantly, as a scientific outcome, e.g. in animal models of disease or safety studies. Developments in the reporting of clinical signs will enhance the scientific value gained from animal experiments and further address the ethical cost. This paper discusses systematic approaches to the observation and reporting of clinical signs in animals (to be) used for research. Glossaries from public and corporate institutions have been consulted and a reference glossary has been set up, providing terminology to be tailored for institutional or project-specific use. The clinical examination of animals must be carried out by competent and specifically trained staff in a systematic way and repeated at adequate intervals and clinical observations must be registered effectively to allow this information to be used. The development of institutional or project-specific glossaries and the use of handwritten records or automated databases are discussed in detail. Among the users are animal care staff, veterinarians and researchers who will need to agree on a given set of clinical signs to be monitored routinely or as a scientific read-out and to train for the proper application. The paper introduces a long list of clinical signs with scientific terminology, descriptions and explanations as a reference glossary to be published and maintained online as a living document supported by the authors as an editorial committee.

Levosimendan improves the initial outcome of cardiopulmonary resuscitation in a swine model of cardiac arrest.

BACKGROUND: Cardiac arrest remains the leading cause of death in Western societies. Advanced Life Support guidelines propose epinephrine (adrenaline) for its treatment. The aim of this study was to assess whether a calcium sensitizer agent, such as levosimendan, administered in combination with epinephrine during cardiopulmonary resuscitation, would improve the initial resuscitation success. METHODS: Ventricular fibrillation was induced in 20 Landrace/Large-White piglets, and left untreated for 8 min. Resuscitation was then attempted with precordial compressions, mechanical ventilation and electrical defibrillation. The animals were randomized into two groups (10 animals each): animals in Group A received saline as placebo (10 ml dilution, bolus) + epinephrine (0.02 mg/kg), and animals in Group B received levosimendan (0.012 mg/kg/10 ml dilution, bolus) + epinephrine (0.02 mg/kg) during cardiopulmonary resuscitation. Electrical defibrillation was attempted after 10 min of ventricular fibrillation. RESULTS: Four animals in Group A showed restoration of spontaneous circulation and 10 in Group B (P = 0.011). The coronary perfusion pressure, saturation of peripheral oxygenation and brain regional oxygen saturation were significantly higher during cardiopulmonary resuscitation in Group B. CONCLUSIONS: A calcium sensitizer agent, when administered during cardiopulmonary resuscitation, significantly improves initial resuscitation success and increases coronary perfusion pressure during cardiopulmonary resuscitation.