白细胞介素—2对离体大鼠心脏的作用及其机理

The purpose of the present study was to explore the biological effects and mechanism of interleukin-2 (IL-2) on the isolated rat heart. The results showed that hrIL-2 increased the number of premature ventricular contraction, heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow in the isolated perfused rat heart. Heat inactivated hrIL-2 had no effect on the heart. Pretreatment with ryanodine canceled the positive effects of hrIL-2 on left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow but had no effects on arrhythmogenesis and tachycardia by hrIL-2. Pretreatment with nifedipine or low extracellular calcium abolished the arrhythmogenic effect of hrIL-2 and attenuated partially the augment of heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow. It suggests that the cardiac activity of hrIL-2 depended on the integrity of its spatial structure and transmembrane influx Ca2+ and intracellularly stored Ca2+ were involved in the cardiac activity of hrIL-2.     

Comparison of exercise effects on the hemodynamics of the Bio 14.6 cardiomyopathic hamster.

1. Comparisons of the effects of 4 and 16 weeks of exercise were made on; cardiac output, stroke volume, heart rate, left intraventricular systolic and diastolic pressures, dP/dt, and heart calcium in the Bio 14.6 cardiomyopathic and F1 B hamsters. 2. In the cardiomyopathic hamster the cardiac output, stroke volume, left intraventricular systolic pressure and dP/dt, which were all depressed in the age related sedentary animals, were increased by both periods of exercise. The left intraventricular diastolic pressure which was elevated was likewise decreased by both exercise periods. Only the 16 week exercise period decreased the resting heart rate. 3. In the normal F1 B hamster, both periods of exercise increased the cardiac output and stroke volume while the left intraventricular systolic pressure was decreased. Only the 16 week exercise decreased the resting heart rate and left intraventricular diastolic pressure and increased the left ventricular dP/dt. 4. Both periods of exercise increased the total heart calcium in the Bio 14.6 hamster while the heart calcium in the F1 B was increased only by the 16 week exercise period.     

The effect of changes in cardiac frequency on left and right ventricular dP/dt max at different contractile states of the myocardium

In 17 canine heart-lung preparations the dependence of frequency potentiation of the right and left ventricular myocardium on the basic inotropic state of the heart was investigated. The effect of unipolar stimulation of the right atrium on dP/dt max in both ventricles was measured. The aortic pressure was maintained constant. Shortly after isolation of the heart, a stepwise increase of rate from 140 to 200 beats/min only had a very weak influence on left ventricular dP/dt max. With deterioration of the myocardium the frequency potentiation of dP/dt max increased considerably. End-diastolic pressure regularly decreased with rising cardiac frequency. Since the real positive inotropic effect is masked by the concomitant fall in diastolic loading, the end-diastolic pressure was maintained constant in a second group of 8 hearts during rate variation. The most pronounced inotropic effect was now found shortly after isolation of the heart. A rate increase of 30 beats/min resulted in a 20% rise of dP/dt max. The frequency potentiation decreased with deterioration of the heart resulting in a 12% dP/dt max increase at an estimated inotropic state of 50% of control. When the contractile state of the heart was improved above the control state by calcium application the frequency potentiation of the myocardium decreased. In the right ventricle similar results were obtained except for the fact that no significant correlation between the steepness of the frequency characteristics and the contractile state of the heart could be found when the end-diastolic pressure was kept constant.     

The effects of changes in heart rate and aortic systolic pressure on left ventricular myocardial oxygen consumption in lambs

To determine whether changes in heart rate and aortic systolic pressure contribute equally to the determination of left ventricular myocardial oxygen consumption, we independently varied heart rate and pressure and compared the resultant oxygen consumption for similar rate-pressure products. In 6 young lambs which underwent atrioventricular node ablation, we varied heart rate by ventricular pacing at 250 beats/min, 300 beats/min, and 120 beats/min while aortic pressure remained stable and varied aortic systolic pressure by infusion of phenylephrine (to 132 +/- 15 mm Hg and 155 +/- 14 mm Hg) and by infusion of sodium nitroprusside (to 79 +/- 6 mm Hg) while heart rate was maintained stable at 200 beats/min. The 3 levels of change in aortic systolic pressure were chosen so that the ratepressure product during the pressure changes matched the rate-pressure product during the heart rate changes. We found that left ventricular myocardial oxygen consumption was the same at all 3 levels of the rate-pressure product whether heart rate was changed and pressure remained stable or pressure was changed and heart rate remained stable. Also, the correlation between oxygen consumption and the rate-pressure product was similar for both heart rate and pressure changes. During nitroprusside infusion at a fixed heart rate, oxygen extraction was significantly lower than during pacing at a heart rate of 120 beats/min when the rate-pressure product was comparable because of the direct vasodilatory effects of nitroprusside. We conclude that heart rate and aortic systolic pressure contribute equally to left ventricular myocardial oxygen consumption at the same rate-pressure product, even though there may be differences in myocardial blood flow and oxygen extraction.     

超声检测左心室舒张功能的临床意义——85例超声检测结果与冠状动脉造影的对照分析

目的超声心动图检测左心室舒张功能与冠状动脉造影对照分析,探讨超声诊断的临床意义。方法85例临床疑诊冠心病超声检查左心室二尖瓣口舒张早、晚期血流充盈速度E、A两峰峰值,计算E/A比值,其结果分为舒张功能正常和降低两组。全部病人均与冠状动脉造影结果对照分析。结果超声检测左心室舒张功能与冠脉造影均正常24例,均异常53例,共77例,符合率90.59%,不符合8例,占9.41%;本文依据冠脉造影提出超声检测左心室舒张功能正常值;并发现冠心病早期舒张功能降低,且随年龄与病程长短不同。结论超声检测左心室舒张功能的改变与冠脉造影符合率高,舒张功能于冠心病早期可降低,随病程长短不同,为临床对冠心病诊治和预防提供有价值的信息。     

Metabolic enzyme response in the pressure-overloaded heart of weanling and adult rats

Weanling and adult rats were subjected to left ventricular pressure overload induced by abdominal aortic constriction. At 5 days or 5 weeks postsurgery, the left ventricle (LV) was dissected, weighed, and metabolic marker enzyme activities (mumole/g/min) of tissue homogenates were measured. Enzymes representing glycolytic (phosphofructokinase (PFK] and mitochondrial (citrate synthase (CS) and malate dehydrogenase (MDH] metabolisms were evaluated. Five days of pressure overload had detectable, but statistically nonsignificant effects on left ventricles of both weanling and adult rats. Sustained pressure overload (5 weeks) increased LV weight by 52 and 39% in weanling and adult rats, respectively. PFK activity was 24 +/- 1 (mean +/- SE) in control weanlings and was unaltered in any of the other groups. LDH isoenzyme composition was estimated by substrate inhibition (ratio 0.33/10 mM pyruvate). With normal heart development, the LDH ratio increased from 1.89 +/- 0.06 to 2.03 +/- 0.08. Pressure overload had no influence on the adult LDH ratio. Developmental LDH responses were not observed in weanling LV after 5 weeks of aortic constriction (1.74 +/- 0.06). The product of CS activity and LV weight was used to estimate mitochondrial mass in the ventricle. Mitochondria accumulated at a rate of about 5% increase per day over the intervening 5-week period of normal heart growth. Pressure overload for 5 weeks in weanling rats elicited net accumulation of mitochondria at a rate of about 9% increase per day. Mitochondrial accumulation in the adapting adult rat heart amounted to less than 1% increase per day. The results indicate that qualitative and quantitative differences exist between young and adult animals in their heart enzyme adaptive responses to pressure overloading. Divergent metabolic adaptations may contribute to heart functional differences in the enlarged heart of weanlings and adults.     

Effect of reserpine upon the haemodynamic course of recovery following experimental myocardial infarction

Acute haemodynamic consequences of coronary artery ligation were evaluated in twenty-four anaesthetized open-chest dogs, nine of which were pretreated with reserpine. The following parameters were measured before, and at 15-min intervals following ligation for at least five hours : ECG, mean arterial blood pressure, aortic blood flow, left ventricular pressure, heart rate, peripheral resistance (P.R.), end-diastolic pressure, dP/dtmax, and "internal work" (I.W. = heart rate x dP/dtmax). It was found that aortic flow was similar in control and reserpine-pretreated dogs (753 +/- 43 vs. 744 +/- 57 ml/min respectively), even though heart rate, blood pressure and other parameters were significantly higher in the control animals. Furthermore, the controls could be divided into two groups : recoverers (R) and non-recoverers (N), on the basis of late stage haemodynamic differences. The ratio of PR/IW taken within one hour of ligation was significantly higher in the R group (496 +/- 69) and reserpine group (479 +/- 30) than in the N group (242 +/- 28), and could predict course of recovery in each dog studied. It is concluded that the presence of myocardial catecholamines may be deleterious to the ischemic heart when the PR or IW are disproportionately altered.     

Hemodynamic effects of pacing-induced tachycardia in valvular aortic stenosis.

The hemodynamic effects of tachycardia were studied in 13 patients with valvular aortic stenosis. Observations were made during sinus rhythm (average heart rate 80 beats/min) and two periods (P1 and P2) when atrial pacing increased the heart rate to 109 and 131 beats/min respectively. The cardiac index did not change, but the left ventricular stroke work index fell from 61.8 to 39.5 g X m/m2 (p less than 0.001) as the heart rate increased. The left ventricular end-diastolic pressure averaged 18 mm Hg during sinus rhythm and fell to about 11.5 mm Hg at P1 and P2 (p less than 0.001). The brachial arterial systolic pressure did not change during pacing, but the left ventricular systolic pressure fell from 208 mm Hg to 201 mm Hg during P1 (p less than 0.05) and 193 mm Hg during P2 (p less than 0.001). The mean systolic aortic valve gradient averaged 64 mm Hg during sinus rhythm and fell to 51 mm Hg during P2 (p less than 0.001), and the peak aortic valve gradient fell from 82 to 69 mm Hg during P2 (p less than 0.001). The left ventricular ejection time fraction increased from 26.9% during sinus rhythm to 31.9% during P1 (p less than 0.05) and 34.7% during P2 (p less than 0.005). Because of the prolonged left ventricular ejection time fraction and smaller stroke volume, a smaller pressure gradient developed across the stenosed valve at higher heart rates. The pacing test was of little value in assessing left ventricular function and thus is not useful during invasive investigations of valvular aortic stenosis.     

Circulatory responses to selective stimulation of medullated and non-medullated fibers of the aortic nerve

Circulatory responses to selective afferent stimulation of medullated and non-medullated fibers in the left aortic nerve were followed in terms of changes in arterial pressure, heart rate, contractile force of the left ventricular fragment and vascular resistance of the hind limb of cats with an opened thorax. Stimulation of the medullated afferents induced a reflex fall of blood pressure mainly by means of decrease in the peripheral vascular resistance, while activation of non-medullated fibers influenced the heart work, i. e. decreased heart rate and myocardial contractile force.     

Influence of a diet rich in fish oil on blood pressure, body weight and cardiac hypertrophy in spontaneously hypertensive rats

The effects of a diet rich in fish oil on arterial blood pressure, body weight, left ventricular weight and heart rate have been investigated in 8 month old spontaneously hypertensive male rats (SHR) as compared to age-matched hypertensive controls. A diet containing 10% fish oil decreased blood pressure by about 40 mmHg within 20 days of starting the experiment, and this effect persisted over the observation period of 80 days. Permitting the animals free access to food, the body weight of the diet group increased by 25%. The degree of hypertrophy as evaluated by relating left ventricular weight to tibial length was significantly reduced (10%) in the diet fed group. Heart rate was increased by 53%. The study demonstrates that a diet rich in fish oil can lower arterial blood pressure over several weeks without a recognizable loss in function despite a considerable increase in body weight. It can be assumed that a more marked regression of left ventricular hypertrophy is counteracted by a reflex increase in sympathetic efferentation to the heart.     

Distension of the pulmonary vein - atrial junctions and plasma vasopressin in the chloralose-anaesthetized dog

The effects of localized distension of the pulmonary vein - left atrial junctions on plasma arginine vasopressin (AVP) have been examined in chloralose anaesthetized dogs. Pulmonary vein distension caused an increase in heart rate and a decrease in plasma AVP concentration. Cooling the vagosympathetic nerves to 10 degrees C caused an increase in arterial pressure and plasma AVP concentration and prevented the changes in heart rate and plasma AVP concentration caused by pulmonary vein distension. Cooling the vagus nerves to 16 degrees C did not change heart rate, arterial pressure, or plasma AVP concentration but significantly reduced the changes in heart rate and plasma AVP concentration caused by pulmonary vein distension. Propranolol (0.5 mg/kg) decreased heart rate and prevented the increase in heart rate associated with pulmonary vein distension but did not abolish the decrease in plasma AVP concentration. It is concluded that distension of the pulmonary vein - left atrial junctions causes a decrease in plasma AVP concentration by stimulating atrial receptors with myelinated afferent fibres. The decrease in plasma AVP concentration is not secondary to the reflex changes in heart rate caused by pulmonary vein distension.     

Longitudinal Hemodynamic Measurements in Swine Heart Failure Using a Fully Implantable Telemetry System

Chronic monitoring of heart rate, blood pressure, and flow in conscious free-roaming large animals can offer considerable opportunity to understand the progression of cardiovascular diseases and can test new diagnostics and therapeutics. The objective of this study was to demonstrate the feasibility of chronic, simultaneous measurement of several hemodynamic parameters (left ventricular pressure, systemic pressure, blood flow velocity, and heart rate) using a totally implantable multichannel telemetry system in swine heart failure models. Two solid-state blood pressure sensors were inserted in the left ventricle and the descending aorta for pressure measurements. Two Doppler probes were placed around the left anterior descending (LAD) and the brachiocephalic arteries for blood flow velocity measurements. Electrocardiographic (ECG) electrodes were attached to the surface of the left ventricle to monitor heart rate. The telemeter body was implanted in the right side of the abdomen under the skin for approximately 4 to 6 weeks. The animals were subjected to various heart failure models, including volume overload (A-V fistula, n = 3), pressure overload (aortic banding, n = 2) and dilated cardiomyopathy (pacing-induced tachycardia, n = 3). Longitudinal changes in hemodynamics were monitored during the progression of the disease. In the pacing-induced tachycardia animals, the systemic blood pressure progressively decreased within the first 2 weeks and returned to baseline levels thereafter. In the aortic banding animals, the pressure progressively increased during the development of the disease. The pressure in the A-V fistula animals only showed a small increase during the first week and remained stable thereafter. The results demonstrated the ability of this telemetry system of long-term, simultaneous monitoring of blood flow, pressure and heart rate in heart failure models, which may offer significant utility for understanding cardiovascular disease progression and treatment.     

Functional state of the left ventricle of the heart in cardiocytotoxic shock]

Changes in the cardiodynamics and the contractile myocardium function under experimental shock caused by intracoronary injection of the anticardial cytotoxic serum were studied on 20 anesthetized dogs. Along with the symptoms of disturbance of the left ventricle function (a decrease of the systolic index, stroke work index of the left ventricle, rate of the intraventricular pressure rise, indices of myocardial contractility, ejection fraction) a decrease of the end-diastolic volume and pressure in the left ventricle was observed. These data show that disturbances in the cardiodynamics were cause not only by the cytotoxic heart damage, but also by derangement of the blood flow to the left heart.     

Rodent Working Heart Model for the Study of Myocardial Performance and Oxygen Consumption

Isolated working heart models have been used to understand the effects of loading conditions, heart rate and medications on myocardial performance in ways that cannot be accomplished in vivo. For example, inotropic medications commonly also affect preload and afterload, precluding load-independent assessments of their myocardial effects in vivo. Additionally, this model allows for sampling of coronary sinus effluent without contamination from systemic venous return, permitting assessment of myocardial oxygen consumption. Further, the advent of miniaturized pressure-volume catheters has allowed for the precise quantification of markers of both systolic and diastolic performance. We describe a model in which the left ventricle can be studied while performing both volume and pressure work under controlled conditions. In this technique, the heart and lungs of a Sprague-Dawley rat (weight 300-500 g) are removed en bloc under general anesthesia. The aorta is dissected free and cannulated for retrograde perfusion with oxygenated Krebs buffer. The pulmonary arteries and veins are ligated and the lungs removed from the preparation. The left atrium is then incised and cannulated using a separate venous cannula, attached to a preload block. Once this is determined to be leak-free, the left heart is loaded and retrograde perfusion stopped, creating the working heart model. The pulmonary artery is incised and cannulated for collection of coronary effluent and determination of myocardial oxygen consumption. A pressure-volume catheter is placed into the left ventricle either retrograde or through apical puncture. If desired, atrial pacing wires can be placed for more precise control of heart rate. This model allows for precise control of preload (using a left atrial pressure block), afterload (using an afterload block), heart rate (using pacing wires) and oxygen tension (using oxygen mixtures within the perfusate).     

Hemodynamic response to laparoscopic cholecystectomy--impacts of increased afterload and ischemic dysfunction of the left ventricle

The authors describe the results of intra-operative hemodynamic monitoring during laparoscopic cholecystectomy in patients with ischemic left ventricular dysfunction and with significant aortic stenosis. The results in the groups composed of 13 and 12 patients were compared with the findings in 10 young, non-obese, non-smokers without significant cardiovascular history and with normal findings during resting transthoracic echocardiography. Monitoring itself was conducted using transesophageal echocardiography 1) after the induction of anesthesia, 2) after the induction of capnoperitoneum, and 3) after setting the operative anti-Trendelenburg position. The measurements were performed at least in triplicate and the results were processed using ANOVA test. Significant differences were identified in the time course patterns of heart rate, mean arterial pressure, dual product (pressure-rate-product), and cardiac output. In terms of pathophysiology, we believe that the most important achievement was the identification of different time course patterns of individual parameters in the respective groups. The results in the group of patients with aortic stenosis were based particularly on the different time course of the mean arterial pressure, while the results in patients with ischemic disease were more dependent on the time course of the heart rate. Very interesting is a drop of peripheral vascular resistance after positioning of these patients which could be explained only partially by a beta-blocking or ACEI medication. In clinical terms, the most important finding was probably that no complications occurred in the entire group of 35 patients, of which 25 suffered from severe organic cardiopathies.     

Atrial natriuretic peptide levels during development of chronic heart failure after myocardial infarction in rats

Serum levels of atrial natriuretic peptide (ANP) are elevated in chronic heart failure presumably due to dilatation of the left atrium resulting from increases in intracardiac pressures. To define the time course of changes in serum ANP levels and to determine the relationship to left ventricular end-diastolic pressure, rats were subjected to coronary artery ligation to produce myocardial infarction and left ventricular failure. Atrial natriuretic peptide levels were measured weekly for four weeks thereafter. In rats with myocardial infarction and elevation of left ventricular end-diastolic pressure there was no change in ANP levels at 7 and 14 days. However, at day 21 and 28, ANP levels were elevated more than 3 fold. There was a correlation between ANP levels and left ventricular end-diastolic pressures. There was no correlation between ANP levels and right atrial pressures or serum sodium concentrations. We conclude that the chronic elevation of left ventricular end-diastolic pressure is required to produce an increase in ANP after myocardial infarction which results in chronic heart failure.     

白细胞介素-2对离体大鼠心脏的作用及其机理

本实验研究免疫调节因子IL-2对心脏的生物学作用及其机制.实验结果显示,hrIL-2增加离体心脏的室性早搏个数,增加心率,影响左室发展压、左室舒张末压和冠脉流量;热失活的hrIL-2对心脏无作用;Ryanodine预处理不改变hrIL-2的致心律失常作用和增加心率的作用,但取消了hrIL-2增加左室发展压、左室舒张末压和冠脉流量的作用;Nifedipine和低钙均取消了hrIL-2的致心律失常作用,部分取消了hrIL-2增加心率、左室发展压、左室舒张末压和冠脉流量的作用.结果提示,IL-2可导致离体心脏心律失常和正性变时变力作用,其心脏作用与其正常的空间结构有关,作用机制涉及跨膜内流钙和胞浆内钙.     

双水平气道内正压通气治疗尿毒症合并左心衰竭患者的疗效观察

目的:观察双水平气道内正压通气(BiPAP)治疗尿毒症合并左心衰竭患者的临床疗效。方法:选取82例确诊为尿毒症合并左心衰竭的患者,在患者进行常规的强心、利尿、扩血管、持续性肾替代治疗(CRRT)30 min后无缓解后,立即对患者进行BiPAP治疗。比较患者在常规治疗30 min末、BiPAP治疗后1 h、2 h后收缩压、舒张压、心率、呼吸频率、二氧化碳分压(PaCO_2)、动脉血氧分压(PaO_2)等指标的变化,以及常规治疗30 min末、BiPAP治疗2h后的血浆脑钠肽(BNP)、血乳酸(Lac)水平和临床表现的变化。结果:经Bi PAP治疗后患者症状和体征缓解的有效率为93.90%。BiPAP治疗1 h、2 h后与常规治疗30 min末比较,患者的收缩压、舒张压、心率、呼吸频率具有显著下降(P0.05),PaO_2则显著升高(P0.05),PaCO_2的变化经比较则无显著的统计学意义(P0.05)。BiPAP治疗2 h后患者的血浆BNP、Lac水平与常规治疗30 min末比较均显著下降(P0.05)。结论:BiPAP治疗尿毒症并发急性左心衰竭患者可有效改善患者的症状和体征,改善心功能,适合在临床上推广应用。     

Beta-adrenoceptor inhibition for induction of acute cardiac failure in pigs

For the testing of heart assist devices most animal models of acute cardiac failure that are usually used show certain disadvantages. We therefore developed a new method using the beta-adrenoceptor antagonist carazolol. We administered a bolus injection of 1 mg/kg followed by a continuous infusion of 1 mg/kg/h in adult German 'Landrasse' pigs. Blood pressure, heart rate, cardiac output and maximum left ventricular pressure rise time showed a significant (P < 0.05) reduction of the control value varying between 40% and 59%. The method is suitable for the testing of surgical approaches in heart failure.     

Left ventricular functional capacity in the endurance-trained rodent

Cardiac myosin P-light chain phosphorylation [P-LC(P)] has been proposed to augment myocardial force production. This study was undertaken to examine the potential for cardiac myosin P-LC(P) for both equivalent heart rate and work load in exercising endurance-trained and nontrained rodents. A 10-wk training protocol elicited a significant reduction in submaximal running O2 uptake while enhancing peak O2 uptake (-17 and 10%, respectively, P less than 0.05). Left ventricular functional index during submaximal exercise, obtained with a high-fidelity Millar ultraminiature pressure transducer, indicated that the trained animals were able to maintain peak left ventricular pressure (LVP) in comparison to their sedentary counterparts, even though both heart rate and rate of LVP development were significantly reduced (P less than 0.05). When expressed on the basis of equivalent submaximal heart rate, peak LVP was augmented in the trained animals. Cardiac myosin P-LC(P) was examined under two conditions known to produce disparate responses in trained vs. sedentary animals. For an equivalent work load, we observed parallel increases in P-LC(P) (20%) and systolic pressure (17%) in both groups, even though the trained animals exhibited significantly lower heart rates (P less than 0.05). For an equivalent heart rate, training evoked a significant increase in systolic pressure (26%, P less than 0.05) and caused a slight increase in P-LC(P) relative to the nontrained controls. Cardiac myosin adenosinetriphosphatase was reduced approximately 10% in the trained animals (P less than 0.05), commensurate with a 2.0-fold increase in the V3 (low adenosinetriphosphatase) isomyosin.(ABSTRACT TRUNCATED AT 250 WORDS)