HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism

Objective To assess the effects of the potassium ATP (KATP) channel blocker HMR1402 (HMR) on systemic and hepato-splanchnic hemodynamics, oxygen exchange and metabolism during hyperdynamic porcine endotoxemia.Design Prospective, randomized, controlled study with repeated measures.Setting Animal laboratory.Subjects Eighteen pigs allocated to receive endotoxin alone (control group, CON, n=10) or endotoxin and HMR (6 mg/kg h^–1, n=8).Interventions Anesthetized, mechanically ventilated, and instrumented pigs receiving continuous i.v. endotoxin were resuscitated with hetastarch to maintain mean arterial pressure (MAP) >60 mmHg. Twelve hours after starting the endotoxin infusion, they received HMR or its vehicle for another 12 h.Results HMR transiently increased MAP by about 15 mmHg, but this effect was only present during the first 1 h of infusion. The HMR decreased cardiac output due to a fall in heart rate, and thereby reduced liver blood flow. While liver O₂ delivery and uptake remained unchanged, HMR induced hyperlactatemia [from 1.5 (1.1; 2.0), 1.4 (1.2; 1.8), and 1.2 (0.8; 2.0) to 3.1 (1.4; 3.2), 3.2 (1.6; 6.5), and 3.0 (1.0; 5.5) mmol/l in the arterial, portal and hepatic venous samples, respectively] and further increased arterial [from 8 (3; 13) to 23 (11; 57); p<0.05], portal [from 9 (4; 14) to 23 (14; 39); p<0.05] and hepatic vein [from 7 (0; 15) to 30 (8; 174), p<0.05] lactate/pyruvate ratios indicating impaired cytosolic redox state.Conclusion The short-term beneficial hemodynamic effects of KATP channel blockers have to be weighted with the detrimental effect on mitochondrial respiration.P. Asfar and Z. Iványi equally contributed to this work     

HTK液心肌保护作用的临床研究

目的:通过对比3种心脏停搏液在风湿性心脏病患者瓣膜置换术中心肌保护的效果,初步评价HTK停搏液的心肌保护作用。方法:将36例因风湿性心脏病接受瓣膜置换术的患者随机分为3组(n=12),分别用St·ThomasⅡ液(A组)、4∶1冷含血停搏液(B组)、HTK液(C组)灌注停跳。于麻醉诱导后、升主动脉开放或心内主要操作完成后5min,术后2、6、12、24、48和72h分别采血检测血清肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)及肌红蛋白(MYO)含量的变化;记录心脏自动复跳率、心律失常发生率、术后正性肌力药物用量、呼吸机支持时间和ICU治疗时间等临床指标;电镜观察心肌细胞超微结构。结果:术后B、C两组血清cTnT(主动脉阻断后5min及术后48、72h除外)、CK-MB(主动脉阻断后5min、术后2h)含量均显著低于A组(P<0.05或P<0.01);两组术后正性肌力药物用量、呼吸机支持时间和ICU治疗时间等临床指标均显著优于A组(P<0.05);两组心肌细胞超微结构的变化显著优于A组(P<0.05),B、C两组比较差异无显著性(P>0.05)。结论:HTK液在瓣膜置换术中具有较好的心肌保护作用。     

Newer P2Y12 Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y₁₂ inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS).Patients and MethodsMEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y₁₂ inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y₁₂ inhibitors and clopidogrel in patients with AMI-CA/CS.ResultsEight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y₁₂ cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies).ConclusionIn patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y₁₂ inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.     

Therapeutic profile of manidipine and lercanidipine in hypertensive patients

Manidipine and lercanidipine are considered effective and safe in the treatment of chronic arterial hypertension and are equipotent in reducing blood pressure (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo runin period, these 2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of the active treatment period, BP was significantly reduced in comparison with the end of the placebo phase in both the manidipine and the lercanidipine groups, without significant differences between the 2 drugs. Daytime BP was significantly reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine, while smaller reductions were seen at nighttime. The smoothness index was the same with both drugs. Unlike lercanidipine, manidipine significantly reduced both basal (-30%) and minimal vascular resistance (-39%), qualifying it as a potent vasodilator. Despite vasodilation, heart rate was not increased but was even slightly reduced by treatment. Ankle-foot edema was observed with both drugs but was less pronounced with manidipine, probably because of greater postcapillary dilatation. In conclusion, manidipine and lercanidipine are both effective and safe in mild-to-moderate essential hypertension, although the former seems to have a more favorable tolerability profile than the latter.     

Color Doppler sonography of orbital and vertebral arteries in migraineurs without aura

PURPOSE: The objective of this study was to investigate whether the retrobulbar hemodynamics in the ophthalmic (OA), posterior ciliary (PCA), central retinal (CRA), and vertebral (VA) arteries are affected in migraineurs without aura. METHODS: The eyes of migraineurs without aura and those of healthy control subjects were evaluated during both headache and headache-free periods. Retrobulbar and vertebral blood flow velocities in the OA, PCA, CRA, and the extracranial part of the VA were measured bilaterally using color Doppler sonography. The peak systolic and end-diastolic flow velocities and the pulsatility (PI) and resistance (RI) indices were determined for all arteries. RESULTS: In total, we enrolled 30 migraineurs and 31 healthy control subjects. Statistically significant differences between headache-free migraineurs and control subjects were observed in the PI and RI of both right and left PCAs and in the RI of both right and left CRAs. The PI and RI of the left VA of the migraineurs were significantly lower during both headache and headache-free periods than were those of the control subjects. Among the migraineurs, the peak systolic and end-diastolic velocities of the left VA were increased during headache periods relative to those found during the headache-free periods. CONCLUSIONS: The retrobulbar circulation and flow hemodynamics in the left VA may be altered in both headache and headache-free periods in migraineurs without aura. The differences found between migraineurs and control subjects may implicate autonomic dysfunction in migraineurs.     

颈动脉连续波多普勒超声评估颅内侧支循环

目的探讨颈动脉连续波多普勒超声评估颅内侧支循环。方法对80例无脑供血动脉狭窄性病变患者，在行颈总动脉压迫试验时采用4MHz连续波探头检测对侧颈内动脉起始段和同侧椎动脉寰枢段血流速度变化。并对连续波多普勒超声与经颅多普勒超声检测的侧支循环方式结果进行比较。结果颈动脉连续波多普勒超声检出前交通动脉侧支开放76例（95％），经颅多普勒超声检出前交通动脉侧支开放76例（95％）。在受检的160个后交通动脉侧支中，颈动脉连续波多普勒超声检出后交通动脉侧支开放140个（88％），经颅多普勒超声检出132个（83％）。结论颅外动脉连续波多普勒超声结合颈总动脉压迫试验检测颅内侧支循环既安全又方便，其准确率与经颅多普勒超声一致。     

不同途径输注鱼精蛋白对先天性心脏病合并肺动脉高压患者体外循环术后血流动力学的影响

目的探讨不同途径输注鱼精蛋白对先天性心脏病合并肺动脉高压患者体外循环术后血流动力学的影响。方法选择手术治疗先天性心脏病患者80例,根据不同给药途径（主动脉、中心静脉）及有无肺动脉高压分为4组,每组20例：A1组（无肺动脉高压、主动脉给药）、A2组（无肺动脉高压、中心静脉给药）、B1组（肺动脉高压、主动脉给药）、B2组（肺动脉高压、中心静脉给药）。记录术前（T0）、输注鱼精蛋白之前（T1）、输注后1min（T2）、3min（T3）、5min（T4）、10min（T5）、15min（T5）、25min（L）各时间点HR、SBP、MAP、CVP等参数,并采静脉血测血清中各时间点组胺的水平。结果输注鱼精蛋白后,经中心静脉给药A,组及B2组MAP、RPP（RHxSBP）均低于主动脉给药A1组（P〈0．05）及B1组（P〈0．01）;B2组CVP明显高于B1组（P〈0．05）。给药后（T2-T7）4组患者血中组胺浓度较术前（T0）均明显升高（P〈0．05）,经中心静脉给药Az组及B2组较主动脉给药A1组及B1组升高更为显著（P〈0．01）。结论先天性心脏病术后经主动脉输注鱼精蛋白可减少组胺的释放;主动脉给药对体外循环术后患者的血流动力学影响较小,特别是合并有肺动脉高压的患者。     

急性脑血管病患者心肌酶谱监测及临床意义研究

目的 探讨急性脑血管病患者心肌酶谱的变化及其临床意义.方法 选择2005年1月-2007年1月期间住院就诊的80例急性脑血管病患者为病例组,同期健康体检人群80例为对照组.病例组于入院1,7,14 d,对照组于体检当日抽血检测各项心肌酶.结果 ①脑出血组与脑梗死组各指标均高于对照组,但脑出血与脑梗死组各指标差异无统计学意义(P＞0.05);有意识障碍组各指标均高于无意识障碍组(P＜0.05);②好转组各指标均低于恶化组(P＜0.05);③好转组第1,7,14 d各指标的水平呈逐渐下降趋势(P＜0.05).结论 急性脑血管病存在心肌酶谱水平的升高,并且心肌酶谱的监测对于病情、预后、治疗情况判断均具有重要的意义.     

Severe QTc prolongation under mild hypothermia treatment and incidence of arrhythmias after cardiac arrest--a prospective study in 34 survivors with continuous Holter ECG

Background

Mild hypothermia treatment (32-34 °C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48 h.

Patients and methods

A total of 34 patients were analysed and received mild therapeutic hypothermia treatment (MTH) according to the current guidelines and irrespective of the initial rhythm. At admission to hospital and in the field in case of OHCA, a 12-lead ECG was performed in all patients.

Results

During cooling the incidence of ventricular tachycardia was low (8.8%) and in none of the patients Torsade de pointes occurred. The QTc interval was within normal range at first patient contact with EMS in the field (440.00 ms; IQR 424.25-476.75; n = 17) but during hypothermia treatment the QTc interval was significantly prolonged at 33 °C after 24 h of cooling (564.47 ms; IQR 512.41-590.00; p = 0.0001; n = 34) and decreased after end of hypothermia to baseline levels (476.74 ms; 448.71-494.97; p = 0.15).

Conclusion

The QTc interval was found to be significantly prolonged during MTH treatment, and some severe prolongations >670 ms were observed, without a higher incidence of life-threatening arrhythmias, especially no Torsade des pointes were detected. However, routine and frequent ECG recording with respect to the QTc interval should become part of any hypothermia standard operation protocol and should be recommended by official guidelines.     

不同侧星状神经节阻滞对心血管反应的影响

目的 :观察左右不同侧SGB对犬心血管反应的影响。方法 :取成犬 2 4只 ,急性闭塞左冠状动脉前降支后 ,随机分为三组。对照组 (6头 ) :不进行SGB ;左侧SGB组 (9头 ) ,右侧SGB组 (9头 ) ,观察相关血液流变学指标变化。结果 :急性左冠状动脉前降支闭塞导致的MOER、RPP的增加 ,左SGB无改善作用 ,并使其进一步增加 ;而右侧SGB后引起HR、CoBF、RPP显著减少。结论 :提示急性心肌梗塞时 ,左SGB有可能使心肌缺血、缺氧恶化 ,而右侧SGB在解除心脏疼痛的同时可减少心肌的耗氧量 ,因而有治疗作用。