Acute hemodynamic effects of ethanol in conscious spontaneously hypertensive and normotensive rats

This study investigated the differential hemodynamic effects of small to high doses of ethanol in conscious age-matched spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). Changes evoked by ethanol (0.25, 0.5, or 1 g/kg, i.v.) or equal volume of saline in mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR) were followed for 90 min in the two rat strains. The baseline MAP (163 +/- 4 vs. 113 +/- 2 mm Hg) of SHRs was significantly (p < 0.05) higher, compared with WKYs due mainly to the presence of an elevated TPR 13.82 +/- 0.12 vs. 2.51 +/- 0.09 mm Hg/ml/min/100 g, p < 0.05) in SHRs. In both rat strains, all doses of ethanol produced immediate increases in MAP at 1 min, after which the MAP responses varied and depended on the rat strain and dose of ethanol used. In WKYs, 0.25 g/kg ethanol had no effect on MAP, but caused significant decreases in CO and SV and increased HR. Ethanol (0.5 and 1 g/kg) produced a short-lived (10 min) and dose-related increase in MAP. The higher dose (1 g/kg) of ethanol elicited significant (p < 0.05) increases in TPR that were counterbalanced by concomitant decreases in CO and SV. In SHRs, the two higher doses (0.5 and 1 g/kg) of ethanol elicited significant (p < 0.05) decreases and increases in MAP, respectively, compared with control (saline-treated) values. The pressor response to the 1 g/kg dose of ethanol was associated with an increase in TPR that achieved a statistical significance (p < 0.05) at 50 and 80 min after ethanol administration. HR was significantly (p < 0.05) reduced by the two higher doses of ethanol, whereas SV and CO were not changed. Blood ethanol concentrations measured 10, 30, and 60 min after ethanol administration were similar in SHRs and WKYs. These findings suggest that acute administration of ethanol to conscious rats elicits hemodynamic responses that are strain- and dose-dependent. In contrast to a short-lived and dose-related pressor response in WKYs, ethanol (0.5 and 1 g/kg) elicited opposite and longer lasting effects on MAP (decreases and increases, respectively) in SHRs. In both rat strains, the pressor response to the higher dose of ethanol was associated with an increase in TPR; an effect that was compromised by a concomitant decrease in CO in WKYs but not SHRs.     

Interferon-gamma-independent CD8+ T cell-mediated protective anti-malaria immunity elicited by recombinant adenovirus

Recombinant adenovirus, expressing the CS protein of Plasmodium yoelii, AdPyCS, was shown to induce a comparable degree of T cell-mediated protection against malaria as a single dose of irradiated P. yoelii sporozoites, causing inhibition of liver stage development. We now report that differently from sporozoite-induced immunity, interferon (IFN)-gamma does not mediate the protective immunity induced by AdPyCS, since a similar degree of protection was observed in AdPyCS immunized mice lacking IFN-gamma-/- and the IFN-gamma receptor (IFN-gammaR-/-) compared to that in wild-type mice. Depletion of CD8+ T cells from these immunized mice almost completely abolished the AdPyCS-induced immunity, indicating that the immunization with AdPyCS induces CD8+ T cell-mediated protective anti-malaria immunity, which is independent of IFN-gamma.     

Transfusion transmitted Yersinia enterocolitica infection in New Zealand

Abstract Aims: To update and summarise cases of transfusion-transmitted Yersinia enterocolitica infection in New Zealand and to evaluate critically suggested methods to reduce this rare but frequently fatal complication of blood transfusion.
Methods: Case reports of four recent transfusion-transmitted Y enterocolitica infections in New Zealand are given and previous reports reviewed. Literature review and evaluation of proposed methods to decrease the incidence of transfusing yersinia contaminated blood.
Results: There have been eight cases of transfusion-transmitted Y enterocolitica infection in New Zealand in the past five years. Four of the five deaths have been directly caused by the transfusion. This gives a transfusion incidence rate of one:65,000 and a fatality rate of one: 104,000 units transfused. This fatality rate is more than 80 times higher than that reported in the United States.
Conclusions: Why the incidence of transfusion-transmitted yersinia is so high is not clear, since we do not store blood as long as many other countries, particularly the United States. In Auckland, however, the cases came at a time when the number of yersinia isolates from the community is reported to be rising.
Many suggestions for the prevention of this problem have been put forward reflecting the fact that there is as yet no perfect solution. Those which are easy to implement and cheap to perform are largely already in place and investigation is continuing into the other alternatives.     

R56865, a Na- and Ca-Overload Inhibitor, Reduces Myocardial Ischemia-Reperfusion Injury in Blood-Perfused Rabbit Hearts

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites or of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 ± 2.8 mmHg in group II and 31.3 ± 8.1 mmHg in group III vs 45.0 ± 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 ± 5.4%, 98.9 ± 6.1%, 85.3 ± 4.8% of baseline values, respectively, in group II, to 64.5 ± 3.0% (P > 0.05), 76.8 ± 3.0%, 70.2 ± 4.0% in group III, vs 52.0 ± 6.5%, 58.9 ± 6.9% and 53.6 ± 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 ± 2.2 ml/min and 19.8 ± 1.8 ml/min in groups II and III vs 14.8 ± 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca²⁺-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.     

Platelet aggregation impacts thrombin generation assessed by calibrated automated thrombography

A calibrated automated thrombogram (CAT) is performed usually with human platelet-free plasma (PFP) but may be more relevant with platelet-rich plasma (PRP). In this case, platelets are not stimulated by subendothelial molecules like collagen. Our aim was to assess the consequence of strong (collagen) or weak (ADP) induction of platelet release and aggregation on thrombin generation. Platelet aggregation in PRP was triggered with 10 µg/mL collagen or 10 µM ADP using a lumi-aggregometer. Thrombin generation curves were monitored by CAT in different conditions: PRP, PRP with activated platelets (actPRP), aggregated PRP (agPRP), aggregated platelets resuspended in autologous PFP (resPRP), PFP and PFP obtained after aggregation (agPFP). We found a 3-fold shortening of the lag time and time to peak and a marked increase in velocity and thrombin peak without changes in endogenous thrombin potential (ETP) in agPRP with both agonists compared with PRP. The same holds true in agPFP but with a marked increase in ETP compared with PFP. Similar changes in the kinetics of thrombin generation were observed with actPRP-collagen and to a lesser extent in resPRP-collagen compared with PRP. By contrast, there were no modifications of the thrombin generation curves in actPRP-ADP. Alpha-2-macroglobin-thrombin complexes were unchanged in the different PRP conditions but were increased in PFP prepared from agPFP compared to control PFP. Platelet aggregation during activation by agonists other than thrombin did not increase thrombin generation but accelerated its kinetics mainly via platelet content release and platelet-derived extracellular vesicules formation. In diseases characterized by altered platelet granule content or release as well as altered platelet activation, a platelet aggregation step prior to CAT analysis may be clinically relevant to improve laboratory estimation of the bleeding/thrombotic balance.     

Cardiovascular responses to physical and psychological stress in female alcoholics with transitory hypertension after early abstinence

BACKGROUND: Male alcoholic patients with acute withdrawal hypertension have shown exaggerated cardiovascular reactivity to stress after 3 to 4 weeks of abstinence, although resting blood pressures (BP) had returned to normal. Studies of this nature, however, have not been extended to women. METHODS: In this study, 32 alcohol-dependent women, abstinent for 4 weeks, were compared with 16 healthy controls on cardiovascular hemodynamics during rest and in response to 2 moderately aversive stressors: isometric handgrip and a speech task. The alcoholics were placed according to withdrawal BP into transitory hypertensive (tHT; n = 16; BP >or=140/90 mm Hg) and normotensive (NT; n = 16; BP <140/90 mm Hg) subgroups. RESULTS: During stress testing, the transitory hypertensive women had increased diastolic BP (p < 0.01), a higher peripheral resistance index (p < 0.05), and a reduced cardiac efficiency index (p < 0.03) relative to the normotensive and control subjects. CONCLUSIONS: This cardiovascular pattern suggests that both cardiac and vascular functions were altered adversely in the transitory hypertensives. In contrast to men examined in previous studies, the transitory hypertensive women had no exaggeration of BP reactivity, but instead showed sustained alterations of resting cardiovascular function in relation to chronic alcohol consumption. Although the pattern of cardiovascular dysregulation seems to be different in female alcoholics than in males, it is consistent with studies showing that cardiovascular effects in women are more severe than in men and emerge at a lower threshold level of chronic drinking.     

Effect of constant light on rhythmic gastric functions in fasting rats

The effects of four weeks of continuous illumination (LL), a subacute stress, on gastric mucosal endogenous aggressive and defensive factors were studied. Young male Sprague-Dawley rats were used with two different illumination regimens: LL and 12 hr light/12 hr dark (LD). At the end of three to four weeks of either regimen of illumination, gastric acid secretion, pepsin secretion, mucus secretion, and potential difference (PD) were studied. All gastric parameters, except mucus secretion, were significantly reduced by LL. The reduction in acid secretion (13.3%) was not significant after Bonferroni correction for the fourt tests Pepsin secretion and PD were 27.9% and 24.6% less, respectively. These differences were significant after Bonferroni correction. The LD rats showed significant circadian rhythms for acid, mucus, and pepsin secretion. The LL rats showed significant rhythmicity for these same parameters with period lengths different from 24 hr. Gross inspection of the gastric mucosa indicated that 69.8% of the LL rats had lesion scores of 1.0 or higher, while none of the LD rats had scores above 0.5.The authors acknowledge the Salt Lake Veterans Administration Medical Center, Department of Research, for support of this study.     

Estimation of Blood Alcohol Concentrations in Young Male Drinkers

This research examined individual differences in the ability to self-monitor the effects of alcohol. Thirty-nine male subjects consumed 0.75 ml/kg alcohol and estimated their blood alcohol concentrations (BACs) at peak BAC and on the ascending and descending limbs of the blood alcohol curve. Family history of alcohol dependence did not affect the accuracy of estimation of BACs. Subjects who reported lower levels of subjective intoxication underestimated their BACs more than did subjects who reported higher levels of subjective intoxication. Subjects with less behavioral impairment underestimated their BACs more than subjects with greater behavioral impairment on the ascending limb of the blood alcohol curve. Accuracy was better on the ascending limb compared with peak BAC and the descending limb, and accuracy became worse over time on the descending limb. It appears that cues to the effects of alcohol rapidly become unavailable on the descending limb, which may contribute to decisions concerning further alcohol consumption and driving after drinking.     

脑络通与绞股蓝总皂甙对动脉粥样硬化性疾病的疗效比较

脑络通是用来治疗动脉粥样硬化性疾病的中药复方制剂,具有滋肾养肝、消痰祛瘀作用。为明确其治疗效果,周脑络通与绞股蓝总甙对103例动脉粥样硬化性疾病患者进行两盲临床对比观察,时间5个月以上。采用美国ATL公司彩色超声多谱勒血流声象系统在用药前后探测患者两侧颈动脉粥样硬化斑块及内中膜厚度,检测患者血脂、超氧化物歧化酶、脂过氧化物和血液流变学指标,部分病人检测血小板聚集率和心功能,并检测患者的血、尿常规和肝、肾功能,观察患者临床症状。结果发现脑络通组57块颈动脉粥样硬化斑块中15.8%(9/57)的斑块消除,47.4%(27/57)的斑块减轻,29.8%(17/57)的斑块不发展,总有效率为93%(53/57);绞股蓝组分别为0%,2.8%(1/36)和47.2%(17/36),总有效率为50%(18/36).脑络通组对斑块的消除、减轻、总有效率及斑块载面积减少方面皆明显优于绞股蓝组(p<0.01或0.05)。脑络通可使增厚的内中膜减薄。在降低血总胆固醇、甘油三酯、低密度脂蛋白、升高血超氧化物歧化酶活性,降低脂过氧化物,降低全血低切粘度、纤维蛋白原、红细胞压积、血小板最大聚集率等方面皆优于绞股蓝组。提示脑络通在调血脂、抗氧化、抗血栓和改善血液流变学等方面均有作用.在临床症状和患者心脏舒缩功能的改善方面亦优于绞股蓝组.本药长期服用对患者血、尿常规,肝、肾功能无异常影响,未见明显毒副反应.说明脑络通治疗动脉粥样硬化性疾病方面疗效优于绞股蓝总皂甙,脑络通可能阻止患者动脉粥样硬化病变的发展,甚至可能使动脉粥样硬化斑块消除。