The influence of chronic exposition to lead on blood pressure

Pri obilasku jedne tvornice akumulatora uočili smo, da su radnici u toj tvornici izloženi mogućnostima jače apsorpcije olova. Sistematske mjerenje koncentracije olova u zraku svih pogona izvršeno je već prije, i tom je prilikom ustanovljeno, da se koncentracija olova u zraku te tvornice kreće od 0-2 mg/m3, a najčešće se koncentracija kretala od 0,2-0,4 mg/ma (5). Uvjeti rada u takvoj atmosferi dali su nam opravdan povod, da vjerujemo, da se radnici s duljim radnim stažom u ovoj tvornici nalaze u uvjetima kronične ekspozicije olovu. Predmet našeg ispitivanja bio je utjecaj kronične ekspozicije olovu na krvni pritisak. Na osnovu pregleda količine izlučenog koproporfirina u urinu, broja bazofilno punktiranih eritrocita u perifernoj krvi i količine olova u krvi izdvojili smo grupu od 46 radnika s najizrazitijim znacima apsorpcije olova i najdužim radnim stažom. Kontrolna grupa se sastojala od 46 radnika jedne tvornice metalne industrije, istih godina starosti, koji u svom proizvodnom procesu ne rade s olovom. Obje su grupe svrstane prema dobi života u 3 skupine, kako to pokazuju tablice I. i II. Kao elementi dokaza za pojačanu apsorpciju olova i kroničnu ekspoziciju uzeti su: koproporfirin u urinu, BpE u perifernoj krvi i količina olova u krvi. Kod kontrolne grupe vršena su ista ispitivanja izuzevši olovo u krvi, jer su vrijednosti koproporfirina u urinu, BpE u perifernoj krvi, kao i sam radni proces pokazivali, da ekspozicija olovu ne postoji.The purpose of this investigation was to find out whether chronic exposition to lead increases the blood pressure. A group of 46 workers in a storage battery factory has been examined. The concentration of lead in air has been previously estimated (Arh. hig. rada, 2 /1951/ 19) to vary from 0-2 mg/m3, most frequently from 0.2--0.4 mg/m3. ln the present investigation the exposition to lead has been measured by the concentration of lead in blood, the coproporphyrine level in urine and the number of stippled cells. The control group consisted of 46 metal workers with no known previous exposition to lead. The same examination have been performed on this group of workers except the determination of lead in blood. Both groups were examined under the same conditions; the experimental and the control group were balanced with respect to age. The measurements of the systolic blood pressure gave an arithmetic mean of 106 mm Hg in the experimental group (exposed to lead) and 116 in the control group. Thus the hypothesis that the chronic exposition to lead increases the blood pressure cannot be accepted on the basis of this evidence

An in vitro evaluation of standard rotational thromboelastography in monitoring of effects of recombinant factor VIIa on coagulopathy induced by hydroxy ethyl starch

BACKGROUND: Rotational thromboelastography (ROTEG) has been proposed as a monitoring tool that can be used to monitor treatment of hemophilia with recombinant factor VIIa (rFVIIa). In these studies special non-standard reagents were used as activators of the coagulation. The aim of this study was to evaluate if standard ROTEG analysis could be used for monitoring of effects of recombinant factor VIIa (rFVIIa) on Hydroxy Ethyl Starch-induced dilutional coagulopathy. METHODS: The study was performed in vitro on healthy volunteers. Prothrombin time (PT) and ROTEG analysis were performed after dilution with 33% hydroxy ethyl starch and also after addition of rFVIIa to the diluted blood. RESULTS: PT was impaired with INR changing from 0.9 before dilution to 1.2 after dilution while addition of rFVIIa to diluted blood lead to an overcorrection of the PT to an International Normalized Ratio (INR) value of 0.6 (p = 0.01). ROTEG activated with the contact activator ellagic acid was impaired by hemodilution (p = 0.01) while addition of rFVIIa had no further effects. ROTEG activated with tissue factor (TF) was also impaired by hemodilution (p = 0.01) while addition of rFVIIa lead to further impairment of the coagulation (p = 0.01). CONCLUSIONS: The parameters affected in the ROTEG analysis were Clot Formation Time and Amplitude after 15 minutes while the Clotting Time was unaffected. We believe these effects to be due to methodological problems when using standard activators of the coagulation in the ROTEG analysis in combination with rFVIIa

Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics?

BACKGROUND: The development of hydroxyethyl starches (HES) with low impact on blood coagulation but higher volume effect compared with the currently used HES solutions is of clinical interest. We hypothesized that high molecular weight, low-substituted HES might possess these properties. METHODS: Thirty pigs were infused with three different HES solutions (20 ml kg(-1)) with the same degree of molar substitution (0.42) but different molecular weights (130, 500 and 900 kDa). Serial blood samples were taken over 24 h and blood coagulation was assessed by Thromboelastograph analysis and analysis of plasma coagulation. In addition, plasma concentration and in vivo molecular weight were determined and pharmacokinetic data were computed based on a two-compartment model. RESULTS: Thromboelastograph analysis and plasma coagulation tests did not reveal a more pronounced alteration of blood coagulation with HES 500 and HES 900 compared with HES 130. In contrast, HES 500 and HES 900 had a greater area under the plasma concentration-time curve [1542 (142) g min litre(-1), P<0.001, 1701 (321) g min litre(-1), P<0.001] than HES 130 [1156 (223) g min litre(-1)] and alpha half life (t(alpha)(1/2)) was longer for HES 500 [53.8 (8.6) min, P<0.01] and HES 900 [57.1 (12.3) min, P<0.01] than for HES 130 [39.9 (10.7) min]. Beta half life (t(beta)(1/2)), however, was similar for all three types of HES [from 332 (100) to 381 (63) min]. CONCLUSIONS: In low-substituted HES, molecular weight is not a key factor in compromising blood coagulation. The longer initial intravascular persistence of high molecular weight low-substituted HES might result in a longer lasting volume effect

N-Acetylcysteine and Allopurinol Synergistically Enhance Cardiac Adiponectin Content and Reduce Myocardial Reperfusion Injury in Diabetic Rats

Background: Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin (APN), an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine (NAC) and/or allopurinol (ALP) can attenuate APN deficiency and myocardial ischemia reperfusion (MI/R) injury in the early stage of diabetes. Methodology/Principal Findings: Control or streptozotocin (STZ)-induced diabetic rats were either untreated (C, D) or treated with NAC (1.5 g/kg/day) or ALP (100 mg/kg/day) or their combination for four weeks starting one week after STZ injection. Plasma and cardiac biochemical parameters were measured after the completion of treatment, and the rats were subjected to MI/R by occluding the left anterior descending artery for 30 min followed by 2 h reperfusion. Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2), reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3) and endothelial nitric oxide synthase (eNOS) but increased IL-6 and TNF-α (all P<0.05 vs. C). NAC but not ALP increased cardiac APN concentrations and AdipoR2 expression in diabetic rats. ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats. Further, NAC and ALP, respectively, decreased postischemic myocardial infarct size and creatinine kinase-MB (CK-MB) release in diabetic rats, while their combination conferred synergistic protective effects. In addition, exposure of cultured rat cardiomyocytes to high glucose resulted in significant reduction of cardiomyocyte APN concentration and AdipoR2 protein expression. APN supplementation restored high glucose induced AdipoR2 reduction in cardiomyocytes. Conclusions/Significance: NAC and ALP synergistically restore myocardial APN and AdipoR2 mediated eNOS activation. This may represent the mechanism through which NAC and ALP combination greatly reduces MI/R injury in early diabetic rats. © 2011 Wang et al.published_or_final_versio

Preconditioning by isoflurane retains its protection against ischemia-reperfusion injury in postinfarct remodeled rat hearts

BACKGROUND: Postinfarct remodeling in the heart may affect protective signaling. We tested whether isoflurane preconditioning retains its protection in postinfarct remodeled hearts. METHODS: Myocardial remodeling was induced by ligation of the left anterior descending coronary artery in male Wistar rats. Six weeks later, diseased hearts were mounted on a Langendorff apparatus and exposed to 40 min of ischemia followed by 90 min of reperfusion. Isoflurane preconditioning was induced with 1.5 MAC (2.1 vol%) isoflurane for 15 min. Infarct size was determined using 1% triphenyltetrazolium chloride staining and corroborated with measurements of lactate dehydrogenase (LDH) release into the perfusate. In some experiments, the protein kinase B and mitochondrial ATP-dependent potassium channel inhibitors LY294002 (10 microM) or 5-hydroxydecanoate (100 microM), respectively, were concomitantly added with isoflurane. Cardiac function was recorded. RESULTS: Six weeks after permanent coronary artery ligation, infarct rats exhibited a markedly increased heart weight/body weight index (5.41 +/- 0.64 vs 3.60 +/- 0.59 g/kg, P < 0.0001) confirming remodeling with compensatory hypertrophy. Isoflurane preconditioning decreased LDH release and reduced infarct size from 32% +/- 6% to 2% +/- 2% (P < 0.0001). Concomitant administration of LY294002 or 5-hydroxydecanoate with isoflurane completely abolished this protection. Functional assessment also showed significant protection from postischemic stunning by isoflurane preconditioning in remodeled hearts, which was lost in the presence of both blockers. CONCLUSIONS: Myocardial preconditioning with isoflurane retains its protection against ischemia/reperfusion injury in postinfarct remodeled rat hearts via similar signaling pathways, as previously reported in healthy hearts

Compromised blood coagulation: an in vitro comparison of hydroxyethyl starch 130/0.4 and hydroxyethyl starch 200/0.5 using thrombelastography

UNLABELLED We compared the effects of progressive in vitro hemodilution (30% and 60%) on blood coagulation in 80 patients receiving one of two different 6% hydroxyethyl starch (HES) solutions using thrombelastography (TEG). The newly developed solution has a mean molecular weight of 130 kD and a degree of substitution, defined as the average number of hydroxyethyl groups per glucose moiety, of 0.4 (HES 130/0.4); the conventional solution has a mean molecular weight of 200 kD and a degree of substitution of 0.5 (HES 200/0.5). Both HES solutions significantly compromised blood coagulation, as seen by an increase in reaction time and coagulation time and a decrease in angle alpha, maximal amplitude, and coagulation index (all P 0.05 for all TEG variables). When analyzing the intrinsic HES effect by taking hemodilution with 0.9% saline into account, progressive hemodilution with both HES solutions resulted in an increasing clot lysis (P < 0.05 after 60 min). Again, there was no difference between HES 130/0.4 and HES 200/0.5 diluted blood. We conclude that HES 130/ 0.4 and HES 200/0.5 compromise blood coagulation to the same degree. IMPLICATIONS Progressive in vitro hemodilution using hydroxyethyl starch (HES) compromises blood coagulation. We observed similar effects of a new HES solution with a mean molecular weight of 130 kD and a degree of substitution of 0.4 (HES 130/0.4), compared with the conventional HES 200/0.5