BACKGROUND AND PURPOSE: Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to date. EXPERIMENTAL APPROACH: Pharmacokinetics, acute effects, and addictive potential in a series of behavioural tests in Wistar rats were performed following subcutaneous (s.c.) administration of DCK (5, 10, and 30 mg·kg-1 ) and its enantiomers S-DCK (10 mg·kg-1 ) and R-DCK (10 mg·kg-1 ). Additionally, activity at human N-methyl-d-aspartate (NMDA) receptors was also evaluated. KEY RESULTS: DCK rapidly crossed the blood brain barrier, with maximum brain levels achieved at 30 min and remaining high at 2 h after administration. Its antagonist activity at NMDA receptors is comparable to that of ketamine with S-DCK being more potent. DCK had stimulatory effects on locomotion, induced place preference, and robustly disrupted PPI. Locomotor stimulant effects tended to disappear more quickly than disruptive effects on PPI. S-DCK had more pronounced stimulatory properties than its R-enantiomer. However, the potency in disrupting PPI was comparable in both enantiomers. CONCLUSION AND IMPLICATIONS: DCK showed similar behavioural and addictive profiles and pharmacodynamics to ketamine, with S-DCK being in general more active. It has a slightly slower pharmacokinetic profile than ketamine, which is consistent with its reported longer duration of action. These findings have implications and significance for understanding the risks associated with illicit use of DCK.

• MeSH
• Behavior, Animal * drug effects   MeSH
• Ketamine * administration & dosage   adverse effects   analogs & derivatives   pharmacokinetics   pharmacology   MeSH
• Rats MeSH
• Locomotion * drug effects   MeSH
• Rats, Wistar MeSH
• Receptors, N-Methyl-D-Aspartate metabolism   MeSH
• Illicit Drugs * adverse effects   pharmacokinetics   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Naphthylpyrovalerone (naphyrone) is a pyrovalerone cathinone that potently inhibits monoamine transporters and provides stimulatory-entactogenic effects. Little is known about the safety of naphyrone or its effects in vivo, and more research is needed to acquire knowledge about its fundamental effects on physiology and behaviour. Our objective was to investigate naphyrone's pharmacokinetics, acute toxicity, hyperthermic potential and stimulatory and psychotomimetic properties in vivo in male Wistar rats. Pharmacokinetics after 1 mg/kg subcutaneous (sc.) naphyrone were measured over 6 h in serum, the brain, liver and lungs. Rectal temperature (degree Celsius) was measured over 10 h in group-versus individually housed rats after 20 mg/kg sc. In the behavioural experiments, 5, 10 or 20 mg/kg of naphyrone was administered 15 or 60 min prior to testing. Stimulation was assessed in the open field, and sensorimotor processing in a prepulse inhibition (PPI) task. Peak concentrations of naphyrone in serum and tissue were reached at 30 min, with a long-lasting elevation in the brain/serum ratio, consistent with observations of lasting hyperlocomotion in the open field and modest increases in body temperature. Administration of 20 mg/kg transiently enhanced PPI. Naphyrone crosses the blood-brain barrier rapidly and is eliminated slowly, and its long-lasting effects correspond to its pharmacokinetics. No specific signs of acute toxicity were observed; therefore, clinical care and harm-reduction guidance should be in line with that available for other stimulants and cathinones.

• MeSH
• Rats MeSH
• Pentanones pharmacokinetics   pharmacology   MeSH
• Rats, Wistar MeSH
• Pyrrolidines pharmacokinetics   pharmacology   MeSH
• Central Nervous System Stimulants pharmacokinetics   pharmacology   MeSH
• Body Temperature drug effects   MeSH
• Body Temperature Regulation drug effects   MeSH
• Illicit Drugs pharmacokinetics   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• Publication type
• Meeting Abstract MeSH

Cíl studie: Endoteliální glykokalyx (EG) hraje ústřední roli v udržení vaskulární integrity a správné funkce mikrocirkulace. Poškození EG u pacientů po úspěšné kardiopulmonální resuscitaci bylo popsáno měřením hladin rozpadových produktů EG (syndekan-1, heparan sulfát). Poměrně novou metodou k hodnocení stavu EG je parametr perfundované hraniční zóny (PBR), který udává v µm boční rozptyl červených krvinek směrem k EG. Cílem této studie bylo zhodnotit změny PBR na zvířecím modelu srdeční zástavy u prasete domácího a zhodnotit použitelnost PBR jako indikátoru poškození EG. Typ studie: Experimentální na zvířecím modelu srdeční zástavy u prasete domácího. Materiál a metody: Srdeční zástava byla indukována nitrosrdeční elektrodou navozením fibrilace komor, která byla léčena defibrilací dle doporučení ERC 2015 po 15 minutách. Sublingvální mikrocirkulace byla vyšetřena ručním mikroskopem fungujícím na principu ortogonálně polarizované spektroskopie. Pořízené nahrávky byly hodnoceny automaticky programem, který poskytl hodnotu PBR. Hodnocení bylo ve třech časových bodech: základní měření (PBR_B), po návratu spontánní cirkulace (PBR_ROSC) a 20 minut poté (PBR_ROSC_20). Výsledky: Hodnoty PBR byly získány od 11 prasat. Hodnoty PBR po ROSC nebyly statisticky signifikantně zvýšeny (p = 0,47). PBR_B bylo 2,129 (± 0,21) µm, PBR_ROSC bylo 2,206 (± 0,27) µm and PBR_ROSC_20 bylo 2,18 (± 0,19) µm. Výsledky jsou ve tvaru průměr (směrodatná odchylka). Závěr: Naše data udávají nevýznamné zvýšení parametru PBR v sublingvální oblasti po srdeční zástavě u prasete. Parametr PBR vyžaduje další testování, než by mohl být zaveden jako neinvazivní parametr udávající míru poškození EG na modelu srdeční zástavy u prasete.

Objective: Endothelial glycocalyx (EG) plays key role in maintaining vascular integrity. Perturbation of the EG in patients after cardiac arrest has been described by measuring syndecan-1 and heparan sulphate levels. Non-invasive method of evaluating EG thickness by using Perfused Boundary Region (PBR) has been introduced recently. PBR represents the amount of lateral deviation of red blood cells towards the EG in µm. The aim of the study was to evaluate changes in PBR on porcine model of cardiac arrest in order to assess the usefulness of PBR as an indicator of glycocalyx damage. Design: Experimental study on a porcine model of cardiac arrest. Material and Methods: Cardiac arrest was induced by intracardiac electrode triggering ventricular fibrillation and treated by defibrillation after 15 minutes in accordance with 2015 ERC guidelines. Sublingual microcirculation was measured by hand-held microscope working on the principle of orthogonal spectral imaging and PBR was computed automatically with specialized software in three timepoints. At baseline (PBR_B), after return of spontaneous circulation (PBR_ROSC) and 20 minutes after ROSC (PBR_ROSC_20). Results: PBR data was obtained from 11 pigs. There was insignificant increase of PBR after ROSC (p = 0.47). The PBR_B was 2.129 (± 0.21), PBR_ROSC was 2.206 (± 0.27) and PBR_ROSC_20 was 2.18 (± 0.19), data are presented as mean and standard deviation. Conclusions: Our data demonstrate insignificant increase of PBR after cardiac arrest in pig. The value of PBR as an indicator of EG shedding requires further study before introducing this parameter as a routine non-invasive tool in pig model of cardiac arrest.

• Keywords
• endoteliální glykokalyx,
• MeSH
• Endothelium, Vascular MeSH
• Glycocalyx * MeSH
• Cardiopulmonary Resuscitation MeSH
• Disease Models, Animal MeSH
• Death, Sudden, Cardiac * MeSH
• Swine MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Cíl studie: Přestože je adrenalin pevnou součástí protokolu pro rozšířenou neodkladnou resuscitaci, jeho úloha je v poslední době zpochybňována. Proto jsme realizovali experiment s cílem posoudit vliv podávání adrenalinu na hemodynamiku během experimentální srdeční zástavy (SZ). Typ studie: Randomizovaná nezaslepená experimentální studie. Typ pracoviště: Experimentální laboratoř v univerzitní nemocnici. Materiál a metoda: U 14 samic prasete domácího byla navozena SZ s fibrilací komor trvající 15 minut (dvě minuty bez resuscitačních pokusů, tři minuty pouze srdeční masáž, deset minut srdeční masáž a umělá plicní ventilace) s následnou defibrilací a sledováním po dobu 20 minut. Před indukcí SZ byla experimentální zvířata randomizována k nitrožilnímu bolusovému podání 15 μg/kg adrenalinu pátou a desátou minutu SZ (skupina A), nebo ke kardiopulmonální resuscitaci bez podávání adrenalinu (skupina B). Protokol byl realizován za kontinuálního monitorování hemodynamických parametrů včetně kalkulace koronárního (CoPP) a cerebrálního perfuzního tlaku (CPP). Výsledky: Ve skupině A byl dosažen návrat spontánní cirkulace u všech 7 zvířat, ve skupině B pouze u 5 zvířat (p = 0,462). Sledované parametry kromě tělesné teploty byly před indukcí SZ v obou skupinách srovnatelné. Podání adrenalinu ve skupině A vedlo k významnému nárůstu CoPP v první minutě po obou podáních ve srovnání se skupinou B (6. minuta: 30,6 ± 6,4 vs. 14,3 ± 3,2 mm Hg; 11. minuta: 29,4 ± 8,5 vs. 12,3 ± 2,4 mm Hg, p < 0,05) s postupným poklesem na původní hodnoty. Ve skupině A jsme pozorovali podobný nárůst CPP bez nežádoucího vzestupu nitrolebního tlaku. Závěr: V našem experimentálním modelu SZ vedlo pravidelné podávání adrenalinu k výraznému dočasnému nárůstu CoPP i CPP bez nežádoucího vzestupu nitrolebního tlaku.

Objective: Although adrenaline administration is a part of the advanced life support algorithm, its role has been questioned recently. Therefore, we conducted a study to investigate the effect of adrenaline administration on the haemodynamics during experimental cardiac arrest (CA). Design: Randomized, unblinded, experimental study. Setting: Experimental laboratory in a university hospital. Materials and methods: Ventricular fibrillation was induced for 15 minutes (two minutes without resuscitation attempts, three minutes of chest compressions, ten minutes of chest compressions and mechanical ventilation) in 14 anaesthetized domestic pigs. After spontaneous circulation was restored, the animals were observed for 20 minutes. Prior to CA induction, the experimental animals were randomized to receive a bolus of 15 μg/kg of adrenaline intravenously (IV) in the 5th and 10th minute of CA (group A) or to undergo cardiopulmonary resuscitation without adrenaline administration (group B). Haemodynamic variables including coronary (CoPP) and cerebral perfusion pressure (CPP) were continuously monitored throughout the protocol. Results: While return of spontaneous circulation was reached in all 7 group A animals, in group B it was achieved in 5 animals only (p=0.462). The observed variables except body temperature were comparable in both the groups prior to the cardiac arrest induction. Administration of adrenaline in group A resulted in a significant increase in CoPP in the first minute after both administrations compared to group B, where adrenaline was not administered (6th minute: 30.6±6.4 vs. 14.3±3.2 mm Hg, 11th minute: 29.4±8.5 vs. 12.3±2.4 mm Hg, p < 0.05) with a gradual decrease to the baseline levels. A similar increase in CPP without undesirable elevation of the intracranial pressure was identified in group A. Conclusion: In our experimental model of CA, regular adrenaline administration resulted in a significant temporary increase in CoPP and CPP without an unfavourable increase of the intracranial pressure.

• Keywords
• experimentální srdeční zástava, cerebrální perfuzní tlak, koronární perfuzní tlak,
• MeSH
• Epinephrine * administration & dosage   pharmacology   adverse effects   MeSH
• Ventricular Fibrillation MeSH
• Hemodynamics * drug effects   MeSH
• Intracranial Pressure drug effects   MeSH
• Cardiopulmonary Resuscitation MeSH
• Coronary Circulation drug effects   MeSH
• Blood Pressure MeSH
• Models, Animal MeSH
• Cerebrovascular Circulation drug effects   MeSH
• Swine MeSH
• Prognosis MeSH
• Randomized Controlled Trials as Topic MeSH
• Advanced Cardiac Life Support * methods   MeSH
• Heart Arrest * drug therapy   therapy   MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

We conducted an experimental study to evaluate the presence of coordinated left ventricular mechanical myocardial activity (LVMA) in two types of experimentally induced cardiac arrest: ventricular fibrillation (VF) and pulseless electrical activity (PEA). Twenty anesthetized domestic pigs were randomized 1:1 either to induction of VF or PEA. They were left in nonresuscitated cardiac arrest until the cessation of LVMA and microcirculation. Surface ECG, presence of LVMA by transthoracic echocardiography and sublingual microcirculation were recorded. One minute after induction of cardiac arrest, LVMA was identified in all experimental animals. In the PEA group, rate of LVMA was of 106+/-12/min. In the VF group, we identified two patterns of LVMA. Six animals exhibited contractions of high frequency (VFhigh group), four of low frequency (VFlow group) (334+/-12 vs. 125+/-32/min, p<0.001). A time from cardiac arrest induction to asystole (19.2+/-7.2 vs. 7.3+/-2.2 vs. 8.3+/-5.5 min, p=0.003), cessation of LVMA (11.3+/-5.6 vs. 4.4+/-0.4 vs. 7.4+/-2.9 min, p=0.027) and cessation of microcirculation (25.3+/-12.6 vs. 13.4+/-2.4 vs. 23.2+/-8.7 min, p=0.050) was significantly longer in VFlow group than in VFhigh and PEA group, respectively. Thus, LVMA is present in both VF and PEA type of induced cardiac arrest and moreover, VF may exhibit various patterns of LVMA.

• MeSH
• Ventricular Fibrillation physiopathology   MeSH
• Swine MeSH
• Heart Ventricles physiopathology   MeSH
• Heart Arrest physiopathology   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH