Drugs acting on the heart: heart failure and coronary insufficiency

Heart failure (HF) and coronary insufficiency are common amongst surgical and critical care patients. Both are chronic conditions interrupted by acute episodes. HF activates neurohormonal mechanisms that worsen renal and cardiac function. Acute heart failure (AHF) commonly presents with dyspnoea as a consequence of systolic and/or diastolic dysfunction. Goals of treatment are symptom relief to maintain tissue perfusion and optimize cardiac function. Diuretics and vasodilators are used early; positive inotropic drugs are reserved for when other treatment has failed. Chronic heart failure (CHF) is treated using changes in lifestyle and drugs to manage symptoms. ACE inhibitors and beta-blockers are effective in systolic heart failure and are associated with improved mortality. HF with preserved ejection fraction (HFPEF) is less responsive to drug therapy, though outcomes are better than for systolic HF. Coronary insufficiency occurs because of an imbalance of myocardial oxygen balance, leading to symptoms of ischaemic heart disease (IHD). Treatment goals are maintaining coronary blood flow and reducing myocardial oxygen demand. Beta-blockers and anti-platelet drugs improve outcomes; modern anti-platelets are more effective but are associated with risks of haemorrhage. Statins are effective for primary and secondary prevention of myocardial infarction; they have additional anti-inflammatory properties.     

2011年与2017年南京市≥25岁居民归因于豆类摄入不足的缺血性心脏病疾病负担研究

目的了解2011年与2017年南京25岁及以上人群归因于豆类摄入不足的缺血性心脏病(IHD)疾病负担和期望寿命损失情况,为IHD的饮食防控策略提供数据支撑。方法本研究资料来源于2011年和2017年南京市慢性病及其危险因素监测、南京市死因监测和2017全球疾病负担(GBD)资料,采用GBD团队提供的Excel插件程序计算人群归因分值(PAF),估算豆类摄入不足导致的IHD死亡和寿命损失。使用SPSS 20.0软件进行t检验。结果2017年,南京市因豆类摄入不足导致IHD的死亡例数占IHD总死亡例数的13.73%,较2011年(12.44%)增长了10.37%。2017年南京市归因于豆类摄入不足的IHD死亡例数和过早死亡损失寿命年(YLL)分别为645例、8116人年,较2011年(449例、6610人年)分别上升43.65%、22.78%;而标化归因死亡率和标化YLL率分别由2011年的11.05/10万、155.72/10万下降至2017年的8.86/10万、118.66/10万,下降率分别为19.82%、23.80%。2017年,豆类摄入不足导致的IHD死亡使期望寿命损失0.17岁,男性、女性分别损失0.13、0.21岁;与2011年相比,2017年男性、女性及总人群归因于豆类摄入不足的期望寿命损失均上升。结论豆类摄入不足已成为影响南京市居民死亡和期望寿命的饮食危险因素之一,应积极倡导合理膳食,增加居民豆类摄入水平,从而减少心血管疾病负担。     

Human Peripheral Eosinophils with Receptors for IgM: Demonstration and Ultrastructural Morphology

Receptors for IgM were detected on peripheral blood human eosinophils by a rosette technique with ox red blood cells coated with the IgM fraction of the specific immunserum. Between 14 % and 43 % (mean 27 %) FcµR positive cells were found after an overnight incubation period at 37°C by using this technique. The specificity of the receptors for IgM was assessed by studying the inhibitory capacity of purified human IgM in the rosette assay. From an ultrastructural point of view, the EA^M rosette-forming cells are mature eosinophlic granulocytes characterized by a nucleus with a variable number of lobes and a certain number of «first type» granules partially or totally devoid of their content.     

胃粘膜内pH值测定在危重病人中的预警价值

目的 :观察在危重病患者中反映组织水平氧代谢的胃粘膜内 p Hi,与反映全身氧代谢的指标间的关系以及胃粘膜内p Hi的预警价值。方法 :用胃张力计测定危重病患者入科即刻及治疗 2 4h后胃粘膜内 p Hi,并测定 p Ha ,Pa O2 / Fi O2 ,行 APACHE 评分。结果 :死亡组入科即刻 p Hi( 7.13 3± 0 .3 74)较存活组 ( 7.3 89± 0 .0 62 )显著降低 ( P<0 .0 1) ,治疗 2 4小时后胃粘膜内 p Hi死亡组( 6.911± 0 .496)较存活组 ( 7.43 4± 0 .0 5 1)降低更显著 ( P<0 .0 0 1) ;入科即刻 p Hi≤ 7.3 2的患者病死率为 75 .0 %,治疗 2 4h后胃粘膜内 p Hi≤ 7.3 2的患者病死率为 88.9%。结论 :作为局部组织氧合指标的 p Hi在常规的全身氧代谢指标未改变之前就发生了明显的变化 ;p Hi的降低与病死率有明显的相关性。     

急性心肌梗塞心肌缺血再灌注损伤18例临床分析

目的：利用间接指标的方法,观察急性心肌梗塞（ＡＭＩ）后心肌再灌注损伤（ＭｙｏｃａｒｄｉａｌＲｅｐｅｒｆｕｓｉｏｎＩｎｊｕｒｙ,ＭＲＩ）的临床表现,了解ＭＲＩ对左室射血功能及梗塞后心绞痛的影响。方法：对尿激酶静脉溶栓后３２例冠脉再通者和１０例冠脉未再通者进行心电图和心肌酶学动态监测,ＡＭＩ后３周所有患者接受心脏彩超检查。结果：临床判断冠脉再通者中ＭＲＩ发生率为５６２５％（１８／３２）,心电图主要表现为突发短暂性ＳＴ段明显抬高,其次是再灌注心律失常,束支或房室传导阻滞最少见。ＭＲＩ时血清ＣＰＫ峰值时间为１３８６±４２６小时,较冠脉再通而无ＭＲＩ组１９１７±５３６小时显著前移（Ｐ＜００５）。ＭＲＩ组ＬＶＥＦ（４５２５±１０７７％）显著高于冠脉未再通组（３８６０±９２５％）（Ｐ＜００５）,但与无ＭＲＩ组（５３２８±１２７７％）相比,Ｐ＞００５。ＭＲＩ组梗塞后心绞痛发生率为２７２８％,与无ＭＲＩ组４２８０％和冠脉未再通组１０００％相比,Ｐ均＞００５。结论：ＡＭＩ静脉溶栓后部分患者发生再灌注损伤,ＭＲＩ对ＬＶＥＦ和梗塞后心绞痛发作无显著影响。     

Conversion factor for comparison of data from Humphrey and Medmont automated perimeters

Background : Clinical experience has shown that the sensitivity indices reported by the Humphrey Field Analyser (HFA) are generally higher than those given by the Medmont Automated Perimeter (M600). It is the purpose of this paper to determine a conversion factor for the two perimeters and to confirm this prediction using clinical data. Theory predicted that HFA_sensitivity ? 5 dB = M600_sensitivity. Methods : Sensitivity versus eccentricity profiles were measured over the central visual field on 10 young subjects using both perimeters. Results : Both the HFA and the M600 operate within the realms of the Weber law and measure similar Weber fractions. The sensitivity profiles had similar slopes (about ?0.2 dB/degree) and were separated by about six decibels with the HFA reporting higher sensitivity values. This result confirmed the theoretical prediction. Conclusion : The difference in threshold sensitivities between the two perimeters is a result of differences in scaling factors and instrument luminances. A suggested clinical conversion factor is to subtract 5 dB from the HFA data to approximate those of the M600.     

Quantification of Mitral and Tricuspid Regurgitation Using Jet Centerline Velocities: An In Vitro Study of Jets in an Ambient Counterflow

A method for quantifying mitral and tricuspid regurgitant volume that utilizes a measure of jet orifice velocity U(0) - m/sec), a distal centerline velocity (U(m) - m/sec), and the intervening distance (X - cm) was recently developed; where jet flow rate (Q(cal) - L/min) is calculated as Q(cal) = (U(m)X)(2)/(26.46U(o)). This method, however, modeled the regurgitant jet as a free jet, whereas many atrial jets are counterflowing jets because of jet opposing intra-atrial flow fields (counterflows). This study concentrated on the feasibility of using the free jet quantification equation in the atrium where ambient flow fields may alter jet centerline velocities and reduce the accuracy of jet flow rate calculations. A 4-cm wide chamber was used to pump counterflows of 0, 4, and 22 cm/sec against jets of 2.3, 4.8, and 6.4 m/sec originating from a 2-mm diameter orifice. For each counterflow-jet combination, jet centerline velocities were measured using laser Doppler anemometry. For free jets (no counterflow), flow rate was calculated with 98% mean accuracy. For all jets in counterflow, the calculation was less accurate as: (i) the ratio of jet orifice velocity to counterflow velocity decreased (U(o)/U(c), where U(c) is counterflow velocity), i.e., the counterflow was relatively more intense, and (ii) centerline measurements were made further from the orifice. But although counterflow lowered jet centerline velocities beneath free jet values, it did so only significantly in the jet's distal portion (X/D > 16, i.e., >16 orifice diameters from the origin of the jet). Thus, the initial portion (X/D < 16) of a jet in counterflow behaved essentially as a free jet. As a result, even in significant counterflow, jet flow rate was calculated with >93% accuracy and >85% for jets typical of mitral and tricuspid regurgitation, respectively. Counterflow lowers jet centerline velocities beneath equivalent free jet values. This effect, however, is most significant in the distal portion of the jet. Therefore, regurgitant jets, although not classically free because of systolic atrial inflow or jet-induced intra-atrial swirling flows, will decay in their initial portions as free jets and thus are candidates for quantification with the centerline technique. (ECHOCARDIOGRAPHY, Volume 13, July 1996)     

The Binding of Cyclosporin A to Human Plasma: An in Vitro Microdialysis Study

Purpose. The human plasma binding of cyclosporin A was studied in vitro using the technique of microdialysis. The effect of temperature on the overall binding interaction between cyclosporin A and human plasma was also investigated. Methods. Flow-through loop-type microdialysis probes were constructed from fused silica tubing and regenerated cellulose tubing with a MWCO of 13000 daltons. Probes were perfused with phosphate buffer (0.5 µl/min) and the concentration of ³H-cyclosporin A in the well-mixed medium (plasma or buffer) was 1200 ng/ml. Relative recoveries of cyclosporin A from plasma or buffer were determined for each probe by separate experiments to measure the solute gain or loss with reference to the perfusate. Results. Recoveries determined by loss were significantly greater than those determined by gain and in each case temperature dependent, with higher recoveries at higher temperatures. The plasma free fraction of cyclosporin A calculated from the recovery data and the perfusate to plasma concentration ratios was dependent on temperature in a log-linear fashion. Mean ± s.d. plasma free fractions expressed in percent were 33.5 ± 4.6, 17.9 ± 3.6, 6.2 ± 0.8, 3.0 ± 0.6, and 1.5 ± 0.2 at temperatures of 4, 10, 20, 30, and 37°C, respectively. Assuming that the enthalpy of binding is constant over the temperature range studied and pseudo-first order conditions exist, the binding reaction at these temperatures was spontaneous, endothermic (H = 74.0 kJ/mole), and entropically driven (S = 0.274 kJ/mole/deg). Conclusions. These results show that the free fraction of cyclosporin A in human plasma is dependent on temperature with the fraction unbound decreasing with temperature in the range of 4 to 37°C. The thermodynamic parameters for the binding of cyclosporin A to plasma components indicate that the reaction is a spontaneous endothermic reaction that is mainly entropy driven, similar to the partitioning of lipophilic molecules from an aqueous to a hydrophobic phase. Moreover, these results show that microdialysis is a feasible method to determine the binding interactions between plasma and cyclosporin A, which indicates the method may be suitable for other difficult binding studies where the solutes have nonspecific binding to separation devices.     

Prognostic significance of the evolution of left ventricular ejection fraction in patients with acute myocardial infarction not treated with thrombolytic therapy

Several controlled trials on the thrombolytic treatment of acutemyocardial infarction (AMI) have failed to demonstrate thatthrombolysis has a simultaneous positive effect on left ventricularfunction and survival. One explanation may be that spontaneouschanges in left ventricular function occurred during the progressionof AMI in control patients. The aim of this study was to evaluatethe spontaneous evolution of left ventricular ejection fraction(LVEF) and its prognostic influence on early (1 month) and late(1 year) mortality in patients with AMI. We studied 216 patientsadmitted to our CCU within 24 h of the onset of symptoms. LVEFwas determined by radionuclide ventriculography on admission(RNV1) and at the end of the necrotic phase (RNV2). Fourteenpatients died before RNV2. On the basis of LVEF values at RNV1,the remaining 202 patients were divided into two groups: thosewith a normal LVEF (55%), and those with an abnormal LVEF (<55%). Among patients with a normal LVEF at RNV1 (64 patients) a significantincrease (>12%) in LVEF at RNV2 was observed in 12.5%, asignificant decrease (>12%) in 12.5% and no change at allin 75%. All of these patients survived, regardless of the evolutionof LVEF. In patients with an abnormal LVEF at RNV1 (138) a significantincrease (>5%) in LVEF at RNV2 was observed in 72.5%, a significantdecrease (>5%) in 6.5% and no change at all in 21%. In patientswith a LVEF increase, both early and late mortality were significantlylower than in patients with a LVEF decrease: (early mortality4% vs 55.5%, P<0.001; late mortality 6% vs 66.6%, P<0.001)respectively. In patients without any LVEF change, mortalitywas significantly lower than in patients with a LVEF decrease:(early mortality 10% vs 55.5%, P = 0.01; late mortality 14%vs 66.6%, P=0.004) respectively. In conclusion, our data demonstrate that a significant increasein LVEF occurs in most patients with an early depression ofleft ventricular function. This behaviour is associated witha low early and late mortality in comparison with the patientswith a LVEF decrease and is independent of thrombolytic treatment.When the early measurement of LVEF is normal the prognosis isnot influenced by LVEF evolution. These findings must be keptin mind when LVEF is used as a prognostic index and as an end-pointfor the evaluation of the effects of thrombolytic therapy.