Determinants of pulmonary blood volume. Effects of acute changes in pulmonary vascular pressures and flow

To examine the effects of pulmonary vascular pressures and flow on pulmonary blood volume (PBV), experiments were performed at constant heart rate and zone 3 conditions (mean left atrial pressure (LAP) above airway pressure) in six anesthetized, open-chest dogs. PBV was calculated as the product of electromagnetic aortic flow and pulmonary mean transit time for ascorbate, obtained without blood withdrawal by polarographic recording of aortic ascorbate changes. In three series of experiments LAP was raised similarly in three steps, from 4.5 to 14.8 mmHg: by mitral constriction which reduced pulmonary blood flow, by blood volume expansion which more than doubled pulmonary blood flow, or by a combination of the two procedures which kept pulmonary blood flow constant. In all three series, LAP and mean pulmonary arterial pressure (PAP) rose in proportion, but PBV was better correlated to PAP (r=0.87±0.02) than to LAP (r=0.66±0.09). These experiments suggest that PAP is the most important factor in determining PBV under zone 3 conditions, whether PAP is raised by increasing pulmonary blood flow or by mitral constriction.     

阿托伐他汀对自发性高血压大鼠心肌组织PPARs表达的影响

目的： 探讨阿托伐他汀对自发性高血压大鼠心肌组织PPARs（peroxisome proliferator-activated receptors, PPARs）表达的影响及其对心肌肥厚的逆转作用与可能机制。方法: 自发性高血压大鼠分为阿托伐他汀灌胃治疗组（SHR-A，30 mg·kg-1·d-1）及模型组（SHR），治疗8周，同周龄Wistar-Kyoto 鼠为正常血压对照组。治疗前及治疗后2、4、8周测量大鼠尾动脉血压。治疗后测血浆血脂水平，以心脏组织病理分析判断心肌肥厚，Western blotting 检测心肌组织PPARα、PPARγ的表达水平。结果: 经过8周治疗， SHR-A组及SHR组血压及血脂水平无明显差异（P＞0.05）。SHR-A组左室重量指数低于SHR组（P＜0.01）。在SHR-A组，PPARα及PPARγ表达高于SHR组（P＜0.01）。结论: 阿托伐他汀显著改善自发性高血压大鼠心肌组织PPARs表达，有效逆转左室肥厚，可能与其降压及降脂作用无关。     

Positive correlation between aortic valve pressure gradient and mitochondrial respiratory chain capacity in hypertrophied human left ventricle

Summary The effect of chronic left ventricular pressure overload on the activities of mitochondrial respiratory chain enzymes was investigated in myocardial biopsies from the left ventricular apex of 13 patients undergoing aortic valve replacement for aortic valve stenosis. Transvalvular pressure gradients measured by left-sided heart catheterization ranged from 52 to 100 mmHg. The specific activity of mitochondrial respiratory chain enzyme complexes I + III (antimycin A sensitive NADH cytochrome c oxidoreductase) and the myocardial concentrations of coenzyme Q₁₀ (CoQ₁₀) increased significantly (P < 0.05) with increasing aortic valve pressure gradient. In contrast, the specific activities of complex IV (cytochrome c oxidase), succinate dehydrogenase, and citrate synthase, a mitochondrial matrix enzyme, showed no significant correlation with the pressure gradient. Since (CoQ₁₀) is the rate-limiting compound of the activity of complexes 1+111 but not of cytochrome c oxidase, succinate dehydrogenase, or citrate synthase, these data suggest that the increase in the activity of complexes I+III is due to the increase in (CoQ₁₀) content.Abbreviations CoQ coenzyme Q - CoQ₉ coenzyme Q₉ - CoQ₁₀ coenzyme Q₁₀ - SDH succinate dehydrogenase - NCP noncollagen protein     

特发性右室心律失常患者血清CMV、CVB病毒抗体分析及其临床意义探讨

目的：通过检测病毒血清抗体,探讨相关病毒感染与特发性右室心律失常（IRVA）发生的相关性.方法：病例对照研究分为3组：IRVA组、其他心脏病平行对照组（Heart-Disease-Control）和健康对照组（Healthy-Control）,每组30例,性别年龄匹配.接受常规检查后进行血清学检查,随访6～12个月.结果：IRVA组与其他2组的X线心胸比值、超声心脏测值比较,无显著性差异（P＞0.05）.3组的柯萨奇B组病毒（CVB）血清IgM阳性率组间差异无显著性;而IRVA组的巨细胞病毒（CMV）血清IgM阳性率（73.3%）显著高于其他2组（P＜0.01）,随访6～12个月后,该组CMV IgM阳性率仍然持续增高（66.7%）.相关性分析发现,CVB感染与IRVA发生的联系强度低（P＞0.05）,而CMV感染与IRVA发生的联系强度高（P＜0.001）.4种常见的病毒血清抗心肌自身抗体检测中发现IRVA组抗β1受体抗体阳性率（60.0%）显著高于其他2组（P＜0.01）.结论：IRVA患者血清CMV IgM阳性率高,该抗体的出现与IRVA的发生高度相关;CMV感染引起IRVA的发生可能与免疫机制（抗β1受体抗体介导）有关.     

Cardiovascular ‘reactivity’ to graded splanchnic nerve stimulation in spontaneously hypertensive and normotensive control rats

Cardiovascular ‘reactivity’ to graded splanchnic nerve stimulations was compared in adult spontaneously hypertensive rats (SHR) and normotensive controls (NCR), during abolished adrenal medullary secretion and neurogenic cardiac control and depressed reflex vascular adjustments. Arterial pressure, heart rate and cardiac output were measured, and total peripheral resistance (TPR) and stroke volume (SV) computed before, during and after nerve stimulation. The neurogenic resistance increases in the major gastrointestinal-renal-hepatic circuits expressed themselves as TPR elevations, which were much accentuated in SHR. This reflects an increased w/r₁ of SHR resistance vessels rather than any altered effector sensitivity, since the responses were particularly accentuated at high discharge rates when noradrenaline junction concentrations approach maximal levels. The splanchnic capacitance responses expressed themselves as SV increases, being the most relevant aspect of capacitance control. SV increased less in SHR, mainly reflecting the reduced diastolic compliance of the hypertrophied SHR left ventricle and the consequent rightward shift of its Frank-Starling curve. The results indicate that an elevated resistance may well be maintained by a normal sympathetic discharge in established SHR hypertension. There seems, however, to be an increasing need for accentuated discharge to the capacitance side to maintain proper cardiac filling of the hypertrophied left ventricle.     

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.     

Regional left ventricular function in the three main coronary artery territories at rest and during exercise

Summary Twenty consecutive patients (mean age 51.6 years) with persistent severe angina pectoris underwent aorto-coronary bypass surgery receiving an overall of 60 anastomosis. On an average, 9.4±1.5 months p.o. first pass radionuclide ventriculograms (18 to 24 mCi 99 m Technetium-Pertechnetate i.v.) were performed at rest and after excerise. Besides measurement of global ejection fraction (GEF), regional ejection fraction (REF) was assessed employing for the first time a new technique: each RAO-view of p.o. radionuclide left ventriculogram was subdivided into three regions according to supply of the three main coronary arteries and their branches as visualized on pre-operative coronary angiogram.GEF improved after maximum exercise in 13 cases by 8.1% points (from 50.4 to 58.5%), remained unchanged three times and decreased four times by 7.1 points (from 51.6 to 44.5%; all changesp<0.05).In completely revascularized regions (n=35) REF improved 24 times by 9.7 points (from 51.1 to 60.8%), did not differ from rest REF six times and decreased in three case by 7.3 points (from 48.6 to 41.3%; all changesp<0.05). Completely revascularized regions responded to exercise like normally perfused areas (increase 7.8 points (from 50.6 to 58.4%;n=7;p<0.05).REF deteriorated in incompletely revascularized regions (n=9) six times by 12.8 points (from 58.0 to 45.2%), remained unchanged twice and improved once by 4.5 points. Total group's REF decreased by 7.3 points (from 56.8 to 49.5%;p<0.05). Exercise REF of incompletely revascularized regions was highly significant inferior to that of completely revascularized regions (49.5 to 58.4%;p<0.01).GEF is a weighted balance of the three regional ejection fractions. The most important parameter is REF of LAD territory.     

Slow inward current in single cells isolated from adult human ventricles

Characteristics of the slow inward current (I _si) in human ventricular myocytes isolated from septal specimens obtained in patients undergoing corrective cardiac surgery were studied using the whole-cell clamp method. A first series of experiments was performed under normal standard superfusion. Clamping from –60 mV evoked an inward current with a threshold at about –35 mV, a maximum around +10 mV and an apparent reversal potential at about +55 mV. No overlapping transient or background outward currents were detected in the –60 to +30 mV potential range, but time-dependent and steady-state outward currents were elicited at potentials above +30 mV. An overlap of steady-state activation and inactivation curves was present between –30 and +10 mV and a slight relief from inactivation was observed for voltages positive to +10mV. The time course of inactivation consisted of fast and slow phases with time constants differing by a factor of eight. Slow time constants of inactivation were shorter at potentials that elicited larger I _si, and longer at potentials inducing smaller I _si. Recovery from inactivation evolved slowly with 100% reactivation occurring in about 4000 ms. Switching the holding potential from –60 to –40 mV led to a reversible decline of I _si without any change of the decay time constants. I _si was significantly increased by 0.1 M isoproterenol. Total or partial inhibition by inorganic (2 mM Mn²⁺, 3 mM Co²⁺, 1 mM Cd²⁺) and organic (1 M methoxyverapamil, 5 M diltiazem) calcium antagonists did not unmask any transient outward current. However, a consistent increase of I _si was reversibly observed with 3 mM 4-aminopyridine while using standard solutions. A second series of experiments carried out with K⁺- and Na⁺-free solutions did not demonstrate any significant change from data observed with standard solutions except a reduction of outward currents at steps above +30 mV and alteration of inactivation kinetics. In this experimental setting, 4-aminopyridine also increased I _si but to a lesser degree. We conclude that I _si, as compared to the outward currents, is dominant in the diseased human ventricular cells we have studied.     

Role of Relative Changes in Caval Flows for Evaluation of Right Atrial Pressure Shifts Induced by Nitroglycerin

Experiments on cats treated with nitroglycerin showed dynamic relationship between changes in caval venous flows: blood flow increased in the superior vena cava and decreased in the inferior vena cava. Blood pressure in the right atrium either decreased, or increased. No significant changes in total venous return were observed during maximum shifts in right atrial pressure, while contractility of the right ventricular myocardium usually decreased. Our findings suggest that the direction of the right atrial pressure shifts induced by nitroglycerin does not depend on venous return, but is determined by the prevalence of flow changes in the superior vena cava or inferior vena cava.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug