双心房输注血管活性药物治疗术后先天性心脏病合并肺动脉高压患儿

目的 探讨经双心房输注血管活性药物在先天性心脏病合并肺动脉高压患儿术后应用的优点和可行性.方法 随机抽取合并肺动脉高压的先天性心脏病90例.一组(45例)经双心房给药,左心房主要输入儿茶酚胺类,右心房输注针对性较强的扩张肺血管药物,如前列腺素E1;另一组(45例)通过中心静脉经右心房给儿茶酚胺类及扩张肺血管药物.以热稀释法测量心排血量(CO)和心指数,计算体循环阻力、肺血管阻力(PVR),经统计学处理后,对该方法进行分析评价.结果 全组患儿术后早期(1周内)死亡3例,均为中心静脉给药组;另有2例完全性肺静脉异位引流术后患儿发生了低心排,1例经左心房给药,另1例经中心静脉给药,经治疗痊愈.无远期死亡.两组患儿体外循环时间及阻断时间无显著差异,血管活性药物的量和时间均无差异(P＞0.05).结论 经双心房输注血管活性药物可明显降低平均肺动脉压及PVR,并可增加CO,较传统的中心静脉给药效果好,对先天性心脏病合并肺动脉高压患儿的治疗有非常重要的意义.双心房给药方法安全可行.     

Depolarization produced by catecholamines in guinea-pig ventricular muscle cells exposed to potassium-rich media and its dependence on temperature

Catecholamines (isoproterenol, adrenaline, and noradrenaline) elicited a small decrease in the resting potential of guinea-pig ventricular muscle cells depolarized by 27 mM K. This catecholamine-induced depolarization (CAD) was enhanced and often led to an automatic activity, when the membrane shunting conductance was reduced by application of 0.05 to 0.2 mM Ba. CAD was blocked by Mn (1 to 2 mM), verapamil (0.5 to 1 X 10(-5) M), and propranolol (0.1 to 1 X 10(-5) M), but not by phentolamine (10(-5) M). CAD did not develop when both Ca and Ba were absent in the bathing solution, but persisted when Sr was present. These results are consistent with the hypothesis that CAD was due at least partly to an increase in the slow channel conductance that was initiated by catecholamine/beta-receptor interaction. CAD was markedly enhanced at low temperatures (21 to 25 degrees C), and such was characterized by slow repolarization after drug withdrawal. Propranolol, when applied after catecholamine, exerted no appreciable effect on this slow repolarization. This beta-blocker abolished CAD at low temperature, if applied prior to catecholamine. Methylxanthines (2 to 5 mM caffeine or theophylline) produced a depolarization similar to that seen with CAD, and the rate of repolarization after drug withdrawal also slowed at low temperature. The slow repolarization of CAD at low temperature appeared to reflect a slowing in the postreceptor metabolic processes responsible for deactivation of the slow channel that was sensitive to beta-receptor stimulation.     

Effects of pheochromocytoma on cardiovascular alpha adrenergic receptor system

Summary We have examined the in vivo consequences of prolonged stimulation of the cardiovascular alpha-adrenergic receptor system in a rat model harboring pheochromocytoma. New England Deaconess Hospital rats with transplanted pheochromocytomas developed systolic hypertension and their plasma norepinephrine concentrations were approximately 60-fold greater than controls. Alpha₁-adrenergic receptors were quantitated in hearts from controls and rats with transplanted pheochromocytoma using the alpha₁-receptor selective antagonist [³H]prazosin. Down-regulation of alpha₁-receptors was found in the hearts of pheochromocytoma rats(33.0 vs. 23.0 fmol/mg protein) without any significant change in the affinities of these receptors for the circulating catecholamine, norepinephrine. Furthermore, the responsiveness of the blood vessel to the alpha-adrenergic stimulation was assessed using in vitro contratile experiments. Aortic rings from pheochromocytoma animals showed an eight fold decrease in sensitivity (EC₅₀) and a 74% decrease in maximal contracility (E_max) to norepinephrine as compared with controls. Similarly, mesenteric artery rings prepared from the same animals showed a five fold loss of EC₅₀ but no decrease in E_max to phenylephrine as compared with controls. In addition, serotonin EC₅₀ and E_max of these mesentery preparations remained unaltered. Coupled with our previous findings [9], the present study suggests that rats with pheochromocytoma secreting large amounts of norepinephrine provide a valuable model system for studying in vivo desensitization of the cardiovascular alpha-receptor systems as well as the beta-adrenergic receptor system.     

Takotsubo triggered by acute myocardial infarction：a common but overlooked syndrome？

Takotsubo cardiomyopathy （TCM） is an acute cardiac syndrome characterized by extensive, but potentially reversible, left ventricular dysfunction in the absence of an explanatory coronary obstruction. Thus, TCM is distinct from coronary artery disease （CAD） and acute myocardial infarction （AMI）. However, substantial evidence for co-existing CAD in some TCM patients exist. Herein, we take this associa-tion one step further and present a case in which the patient simultaneously suffered from AMI and TCM, and in which we believe that a primary coronary event triggered TCM. An 88-year-old female presented with chest pain. Echocardiography revealed apical akinesia with hypercontractile bases. An occluded diagonal branch with suspected acute plaque rupture was identified on the angiogram, but could not explain the extent of akinesia. Cardiac function recovered completely. Thus, this patient adhered to current diagnostic criteria for TCM. TCM is a well-known complication for other conditions associated with somatic stress. It is therefore intuitive to assume that AMI, which also associates with somatic stress and elevated catecholamine, can cause TCM. Our case illustrates that TCM and AMI may occur simulta-neously. Although causality cannot be conclusively inferred from this association, the somatic stress associated with AMI may have caused TCM in this patient.     

In vivo regulation of phenylalanine hydroxylase in the genetic mutant hph-1 mouse model

The hph-1 mouse has low liver activity of GTP cyclohydrolase 1, the rate limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH₄). BH₄ is the cofactor for phenylalanine hydroxylase (PAH) and in the early stages of life the hph-1 mouse is hyperphenylalaninemic. At approximately 15 days after birth the blood phenylalanine levels normalize. During this period the animals provide an in vivo model which can be used to study the regulatory effects of phenylalanine on PAH, and for related pediatric metabolic disease in humans; from birth to youth. We therefore, examined; liver PAH activity using BH₄ and 6-methyltetrahydropterin (6MPH₄) as cofactor; PAH total enzyme concentration by Western blotting using the PH8 antibody, and PAH state of phosphorylation using the PH7 antibody from 4 to 18 days after birth. The findings were compared to the wild type animals that are not hyperphenylalaninemic during this period. PAH (6MPH₄) activity and total protein (PH8 antibody) rose steadily in the hph-1 mice. In control mice, both activity and total protein fluctuated. The degree of phosphorylation of PAH in the mutants and the state of activation (as measured by the 6MPH₄/BH₄ activity ratio) increased as phenylalanine levels rose, and decreased when they fell. Similar patterns were not seen in the control animals. These studies provide in vivo evidence that phenylalanine concentration regulates the activity of PAH in the hph-1 mouse and that this acts via a mechanism that includes phosphorylation of the PAH molecule. The kinetic values (K_m and V_max) for mouse PAH are also reported.     

Early vasopressin reduces incidence of new onset arrhythmias

Purpose

The objective of this study was to determine the effect of early vs late vasopressin therapy on catecholamine dose and duration.

Materials and methods

We conducted a single-center, retrospective chart review of adult patients admitted to the medical intensive care unit between January 2010 and December 2011 with septic shock requiring catecholamine and vasopressin therapy. Patients were included in the early group if vasopressin was initiated within 6 hours and the late group if vasopressin was initiated between 6 and 48 hours of catecholamine(s).

Results

Duration of catecholamine and vasopressin therapy was similar between the 35 patients in the early group and the 36 in the late group. Vasopressin therapy was associated with a decrease in catecholamine requirements in both groups. Early vasopressin was associated with fewer new onset arrhythmias (37.1% vs 62.9%, P < .001). There was no difference in mortality, hospital, or intensive care unit length of stay between the early and late group vasopressin groups (88.6% vs 88.9%, P = 1; 14 vs 10 days, P = .48; 9 vs 7 days, P = .71, respectively).

Conclusions

Early initiation of vasopressin therapy in adult critically ill patients with septic shock was associated with no difference in total catecholamine requirements but decreased incidence of new onset arrhythmias.     

Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner

Background

Takotsubo cardiomyopathy (TCM) is characterized by regional left ventricular dysfunction that cannot be explained by an occlusive lesion in a coronary artery. Catecholamines are implicated in the pathogenesis of TCM but the mechanisms involved are unknown. Because the endogenous and the most commonly used exogenous catecholamines have well defined adrenoceptor subtype affinities, inferences can be made about the importance of each adrenoceptor subtype based on the ability of different catecholamines to induce TCM. We therefore studied which of five well-known catecholamines, that differ in receptor subtype affinity, are able to induce TCM-like cardiac dysfunction in the rat.

Methods

255 rats received intraperitoneally isoprenaline (β₁/β₂-adrenoceptor agonist), epinephrine (β₁/β₂/α-adrenoceptor agonist), norepinephrine (β₁/α-adrenoceptor agonist), dopamine (α/β₁/β₂-adrenoceptor agonist) or phenylephrine (α-adrenoceptor agonist). Each catecholamine was given in five different doses. We measured blood pressure through a catheter inserted in the right carotid artery and studied cardiac morphology and function by echocardiography.

Results

All catecholamines induced takotsubo-like cardiac dysfunction. Isoprenaline induced low blood pressure and predominantly apical dysfunction whereas the other catecholamines induced high blood pressure and basal dysfunction. In another set of experiments, we continuously infused hydralazine or nitroprusside to rats that received epinephrine or norepinephrine to maintain systolic blood pressure < 120 mm Hg. These rats developed akinesia of the apex instead of the base. Infusion of phenylephrine to maintain blood pressure > 120 mm Hg after isoprenaline administration prevented apical TCM-like dysfunction.

Conclusions

Catecholamine-induced takotsubo-like cardiac dysfunction appears to be afterload dependent rather than depend on stimulation of a specific adrenergic receptor subtype.     

慢性充血性心力衰竭患者心率变异性与病情的相关性分析

目的：为探讨心力衰竭（心衰）患者心率变异性与病情的关系。方法：本文采用时域及频域２种分析方法，对９２例心衰患者和５１例对照组健康人进行了心率变异性对比分析，并对部分患者（ｎ＝１０）及对照组健康人（ｎ＝２０）进行血浆儿茶酚胺（去甲肾上腺素、肾上腺素）浓度测定及心率变异性随访。结果：心衰患者的心率变异性显著低于对照组健康人；并且与病情及心功能明显相关（Ｐ＜０．０５～０．００１）；心衰患者中近期死亡者心率变异性进一步降低（Ｐ＜０．０５～０．００１）；心衰患者血浆去甲肾上腺素及肾上腺素浓度明显高于健康组（Ｐ＜０．０２～０．０１）。结论：心衰患者心率变异性降低提示，心衰患者心率变异性的数量变化，反应患者病情变化。高的血浆儿茶酚胺浓度间接说明了心衰患者心脏自主神经功能受损是神经激素系统持续激活的结果