Relationship among cardiac output, shunt, and inspired O2 concentration.

In comparing gas exchange responses of the methacholine- (MCh) challenged mongrel dog with leukotriene receptor blockers and placebo at different inspiratory O2 fractions (FIO2), we previously noted systematically different values of cardiac output as a function of drug administration and/or FIO2. This confounds identification of the effects of FIO2 and/or drugs on gas exchange, because shunt is well known to vary directly with cardiac output when other factors are equal. Accordingly, in six dogs we examined the dependence of combined shunt and low ventilation-perfusion (VA/Q) blood flow ("shunt") on cardiac output in the MCh-challenged mongrel dog. Two dogs breathed 100% O2, another two breathed room air, and the final pair breathed 12% O2 while cardiac output was altered several times by sequentially opening and closing arteriovenous fistulas every 10 min for approximately 90 min after a standard MCh challenge. On 100% O2, shunt increased by 11.0% of the cardiac output per 1-l/min increase in cardiac output. On room air, the value was 7.4%. With 12% O2 breathing shunt rose by only 2.2% per 1-l/min rise in blood flow. This FIO2 -dependent behavior of the shunt-cardiac output relationship was highly reproducible, both within and between animals. It suggests that the increase in shunt with cardiac output depends more on vascular tone of noninjured areas than on tone of the low VA/Q regions (which are hypoxic at all FIO2 values).     

Effect of using nifedipine by patients with chronic congestive heart failure treated with digoxin and furosemide

Nifedipine was administrated to 25 patients with chronic congestive heart failure treated with digoxin and furosemide++, nifedipine (NF) in a daily dose of 30-80 mg for 14 days. Before and after the treatment with nifedipine chest X-ray, blood biochemical investigations, echocardiographic evaluation of the left ventricular function and submaximal exercise test were performed. Nifedipine induced significant decreases in the left ventricular systolic dimension, heart volume, blood serum potassium and uric acid concentrations and hematocrit . Resting and exertional heart rate, blood pressure, exercise power and duration, watt-pulse, myocardial oxygen demand index, ejection fraction, cardiac output, body weight, 24-hour urinary output, blood serum concentrations of urea, creatinine, sodium and chloride changed insignificantly following nifedipine administration. The obtained results suggest that long-term nifedipine treatment of patients who were already given digoxin and furosemide neither improve nor worsen their clinical status.     

芪苈强心胶囊辅助治疗老年慢性心力衰竭的临床研究

目的：探讨芪苈强心胶囊辅助治疗老年慢性心力衰竭的临床疗效及其安全性。方法：选择我科2012年1月．6月收治的102例老年慢性心力衰竭患者为研究对象,并将其随机分为两组,对照组42例,给予西医常规治疗及地高辛0．125mg／d;观察组60例,在对照组基础上将地高辛用量改为O．0625mg／d,并予芪苈强心胶囊,每次4粒,每日3次12服,2个月为1个疗程,治疗3个疗程后观察和比较两组心功能的变化。结果：观察组和对照组的治疗总有效率分别为95．0．％和78．6％,观察组显著高于对照组,两组比较差异有统计学意义（P〈0．05）;观察组的平均住院时间明显短于对照组（P〈0．05）。治疗后,两组心输出量（cO）、每搏输出量（SV）、左室射血分数（LVEF）舒张晚期与舒张早期充盈速度比（～E）均较治疗前明显升高（P〈0．05）,而脑钠肽（BNP）水平较治疗前显著降低（P〈O．05）,且观察组CO、SV水平均明显高于对照组（P〈0．05）,BNP水平明显低于对照组（P〈0．05）。治疗过程中,对照组发生洋地黄中毒3例,观察组无不良事件发生。结论：芪苈强心胶囊辅助治疗老年慢性心力衰竭可有效改善其心功能,并减少地高辛用量和洋地黄中毒的发生,值得临床推广应用。     

Systemic and regional hemodynamic reactions to metabolic stress caused by 2-deoxyglucose

Changes in parameters of systemic and regional hemodynamic, elicited by intraarterial administration of 250 or 500 mg/kg of 2-deoxy-D-glucose (2-DG) were studied in the awake Wistar rats with microsphere technique. Measurements were performed before, 15-and 40-min after 2-DG administration. Significant decrease in the heart rate as well as increase in stroke volume were observed 15 min after 2-DG. It was a tendency to increase in cardiac output. Blood flow in skin and skeletal muscles were decreased whereas in the brain, heart, adrenal glands and small intestine there were significant increases in the blood flow. We conclude that hemodynamic responses to 2-DG reflect the effects of humoral (adrenaline) and central sympathetic factors.     

Contributions of hemodynamic monitoring to the treatment of chronic congestive heart failure.

Optimal therapy for congestive cardiac failure requires identification of correctable factors that aggravate it as well as an understanding of its etiology. Increased sympathetic nervous system activity, reduced renal blood flow, and cardiac hypertrophy and dilation are the main compensatory processes that occur in response to cardiac failure. Although they may be of initial benefit in supporting a reduced stroke volume, they may ultimately prove self-defeating. New drugs for the treatment of severe congestive heart failure include dopamine, which has a selective nonadrenergic dilator effect on the renal vascular bed, and dobutamine, which has potent inotropic effects, lowers the left ventricular filling pressure and does not increase the heart rate or the systemic vascular resistance. By reducing both the resistance to left ventricular ejection and the venous return to the right heart, vasodilators result in improved peripheral perfusion and reduced pulmonary congestion. Optimal therapy for refractory cardiac failure can be rationally determined by characterizing the hemodynamic profile through measurement of the mean arterial pressure, the left ventricular filling pressure, the cardiac output and the systemic vascular resistance. The specific therapy can then be effectively and safely delivered by a careful analysis of the dose-response relation as identified by hemodynamic monitoring.     

Circulatory and Metabolic Effects of Oxygen in Myocardial Infarction

The circulatory and metabolic effects of inhalation of oxygen in high concentration were investigated in 50 patients with acute myocardial infarction. The heart rate, arterial blood pressure, cardiac out-put, blood gas tensions, pH, and lactate and pyruvate levels were measured. In general, oxygen inhalation produced a fall in cardiac output and stroke volume and a rise in blood pressure and systemic vascular resistance. In a small number of patients with very low cardiac out-puts there was a rise in output. A substantial rise in arterial oxygen tension was obtained even in patients with low initial values. The raised arterial blood lactate levels which were frequently present were reduced after oxygen. The therapeutic implications of these effects are discussed.     

Decreased O2 consumption and cardiac output during normobaric hyperoxia in conscious dogs

Recent reports indicate that under certain restricted conditions hyperoxia may decrease tissue O2 consumption. However, this effect has not been established for whole body O2 consumption in the intact healthy conscious state. The goal of the present study was to document the effect of hyperoxia on resting whole body O2 consumption and hemodynamics under these latter more general physiological conditions. The inspired gas was delivered by mask to six fasted resting conscious dogs and alternated hourly between air and O2-enriched air (hyperoxia) for 5 h, while hemodynamics and blood gas data were obtained every 20 min. Compared with air breathing, hyperoxia increased the mean arterial O2 tension from 95 to 475 Torr and decreased heart rate, cardiac output, pulmonary vascular resistance, and right and left ventricular work rates and thus, presumably, myocardial O2 consumption. Hyperoxia also increased systemic vascular resistance and right atrial pressure but did not change stroke volume or systemic arterial pressure. The increase in arterial O2 content during hyperoxia was counterbalanced by the decrease in cardiac output, so that O2 delivery was unchanged by hyperoxia. Surprisingly, hyperoxia decreased the arterial-to-mixed venous difference in O2 content; this decrease together with the decrease in cardiac output produced a decrease in resting whole body O2 consumption from 5.88 +/- 0.68 to 4.80 +/- 0.62 ml O2.min-1.kg-1 (P = 0.0002). It is concluded that under physiological conditions normobaric hyperoxia may decrease metabolic rate in addition to cardiac output, which may have important implications for the metabolic regulation of O2 utilization as well as for the medical and nonmedical uses of O2.     

Effect of graduated embolization of the coronary vessels using microspheres on the pumping function and contractility of the left ventricle in rats

Left ventricle (LV) function and systemic hemodynamic changes after coronary artery embolization by 15 microns radioactive microspheres were studied in anesthetized rats. Selective coronary embolization was produced by microsphere injection during ascending aorta occlusion in closed chest animal by using "L"-shaped wire. Maximal pressure (Pmax) developed was evaluated during ascending aorta occlusion. Coronary embolization evoked dose-dependent reduction in Pmax and dP/dtmax and then decrease in basal LV systolic pressure. dP/dt/P, with parallel increase in end diastolic LV pressure. Changes of cardiac output were bidirectional: after administration of relatively small amount of microspheres cardiac output increased. This method can be used for producing quantitative myocardial ischemia and we suggest that it may be a suitable model of the chronic heart failure.     

Cardiac resynchronization therapy modulation of exercise left ventricular function and pulmonary O₂ uptake in heart failure

To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P < 0.05). During moderate-intensity exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P < 0.05), and steady-state stroke volume increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P < 0.05). LV end-diastolic volume did not change from rest to steady-state exercise post-CRT (P > 0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P < 0.05). For peak exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P < 0.05). The increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P < 0.05). These findings demonstrate the chronic CRT-mediated cardiac factors that contribute, in part, to the speeding in Vo(2) kinetics and increase in peak Vo(2) in clinically stable heart failure patients.     

Recovery rate of the cardiovascular system in rabbits following short-term halothane anesthesia.

Mean arterial pressure, cardiac output and heart rate were determined in eight male New Zealand white rabbits while conscious and after being anesthetized with halothane plus nitrous oxide for 15 minutes. Delivery of the anesthetic agent was stopped and the measurement repeated at 15, 30, 60 and 210 minutes. In a separate experiment blood samples were obtained for plasma renin activity in six rabbits before anesthesia, after 15 minutes of halothane plus nitrous oxide administration, and again 210 minutes after cessation of the anesthesia. Later, this experiment was repeated with the same rabbits except that they were allowed to breathe room air instead of the anesthesia. The halothane anesthesia resulted in decreased mean arterial pressure and cardiac output, but these returned to the preanesthetic levels by 15 minutes after stopping the anesthesia. Heart rate increased during halothane administration, and although it tended to return toward control levels after cessation of the halothane, heart rate was still elevated 210 minutes later. Halothane plus nitrous oxide produced an increase in plasma renin activity, which then subsided to normal by 210 minutes following anesthesia; breathing room air did not result in increases in plasma renin activity. These studies revealed that although short-term anesthesia with halothane plus nitrous oxide resulted in cardiovascular changes in rabbits, after cessation of the anesthetic agent the cardiovascular system quickly returned to normal.     

Continuous negative extrathoracic pressure combined with high-frequency oscillation improves oxygenation with less impact on blood pressure than high-frequency oscillation alone in a rabbit model of surfactant depletion

Background  

Negative air pressure ventilation has been used to maintain adequate functional residual capacity in patients with chronic muscular disease and to decrease transpulmonary pressure and improve cardiac output during right heart surgery. High-frequency oscillation (HFO) exerts beneficial effects on gas exchange in neonates with acute respiratory failure. We examined whether continuous negative extrathoracic pressure (CNEP) combined with HFO would be effective for treating acute respiratory failure in an animal model.     

Effects of induced bronchoconstriction on pulmonary blood flow

Allergic bronchoconstriction may be associated with hemodynamic alterations due to changes in respiratory mechanics (or the associated changes in arterial blood gas composition) or the cardiovascular effects of chemical mediators. In an attempt to differentiate between these two possible mechanisms, we obtained measurements of hemodynamics, respiratory mechanics, and O2 consumption (VO2) in nine asymptomatic adult ragweed asthmatics before and after inhalation challenge with either ragweed extract or methacholine. We measured specific airway conductance (sGaw) by body plethysmography, pleural pressure with an esophageal balloon catheter, pulmonary blood flow (Q) and VO2 by a rebreathing technique, and heart rate. For a similar degree of bronchoconstriction after the two types of challenge (mean +/- SD sGaw 0.06 +/- 0.03 and 0.05 +/- 0.02 cmH2O-1 . s-1, P = NS), mean Q increased by 29 and 29%, and mean VO2 by 33 and 37% 15-20 min after ragweed and methacholine, respectively. Since heart rate did not change, there was a concomitant increase in mean stroke volume by 25 and 35%, respectively (P less than 0.05). The respiratory pleural pressure swings during quiet breathing and the rebreathing maneuver and the work of breathing during rebreathing also increased to a similar degree after the two types of challenge. These observations suggest that, if chemical mediators are released into the circulation during antigen-induced bronchoconstriction, their blood concentrations are too low for appreciable cardiovascular effects. The increase in rebreathing cardiac output during allergic and nonallergic bronchoconstriction is probably due to increases in intrathoracic pressure swings and in the work of breathing.     

Interactions of respiration and the bradycardia of submersion in harbor seals.

Six harbor seals with percutaneous tracheostomies were artificially ventilated while immersed. Changes in the oxygen content of the inspired gas and in the minute-volume altered the magnitude of the bradycardia observed after the animal had been submerged for 30 s. The average heart rate in five seals changed from 16.7 (S.D. = 4.4) beats per minute during artificial ventilation with N2, to 58.7 (S.D. = 10.4) beats per minute while breathing air, but this cardiac chronotropic effect of oxygen was blocked by addition of 7% CO2 to the inspired gas. Ventilatory minute-volumes above approximately 3 litres/min caused cardiac acceleration in a manner related to ventilation; below this, changes in heart rate were inconsistent. While being artificially ventilated with air, the average heart rate in five seals changed from 16.5 beats per minute to 73.4 beats per minute as ventilation was increased from 0 to greater than 8 litres/min. These experiments demonstrate that O2, CO2, and ventilatory minute-volume have significant effects upon the heart rate of seals under water and suggest the presence of chemoreceptor-mediated effects on heart rate during submersion.     

Hemodynamic and biochemical effects of 100% oxygen breathing in humans.

High concentrations of inspired oxygen have been reported to have significant hemodynamic effects that may be related to increased free radical production. If oxygen therapy increases free radical production, it may also modify hemodynamic responses to a nitric oxide donor. Twenty-nine healthy male volunteers were studied using randomized, double-blind, placebo-controlled, crossover designs to determine whether oxygen therapy is associated with hemodynamic and forearm vascular effects. We measured hemodynamic parameters and forearm vascular responses before and 1 h after exposure to 100% oxygen versus medical air. Plasma 8-iso-PGF2alpha and plasma vitamin C were measured to assess the biochemical effects of oxygen administration. Hemodynamic measurements were also made following the acute administration of sublingual nitroglycerin. Oxygen therapy caused no significant change in blood pressure, plasma 8-iso-PGF2alpha, or vitamin C. Oxygen did cause a significant reduction in heart rate and forearm blood flow, and an increase in peripheral vascular resistance. Oxygen caused no change in the hemodynamic response to nitroglycerin. Therefore, in healthy young adults, therapy with 100% oxygen does not affect blood pressure, despite causing an increase in vascular resistance, is not associated with evidence of increased free radical injury, and does not affect the hemodynamic responses to nitroglycerin.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Non-invasive echocardiographic studies in mice: influence of anesthetic regimen.

Transgenic murine models of cardiovascular disease offer great potential insights regarding mechanisms of human disease, but efficient and reliable methods for phenotype evaluation are necessary. We employed non-invasive echocardiography to evaluate hemodynamic parameters in mice, and evaluated statistical reliability of these parameters with respect to anesthesia regimen. Male CF-1 mice received inhaled halothane (0.25-0.75% in 95% O2) or ketamine/xylazine (80/10 mg/kg i.p.) and 2-dimensional, M-mode, and Doppler ultrasound imaging were used to assess cardiac contractility and aortic flow velocities. Halothane was more convenient and reliable with respect to rate of induction, reversal, and control of anesthetic depth. At comparable levels of anesthesia, ketamine/xylazine produced significant reductions in heart rate (308 +/- 14 vs. 501 +/- 14 bpm, p<0.001), left ventricular fractional shortening (41.7 +/- 1.3 vs. 49.3 +/- 1.0%, p<0.001), and cardiac output (7.6 +/- 0.5 vs. 11.5 +/- 0.6 ml/min, p<0.001) when compared to halothane inhalation. No change in stroke volume or peak aortic velocity was observed. Correlation analyses revealed highly significant positive relationships between heart rate and fractional shortening (r=0.61, p<0.002) and cardiac output (r=0.88, p<0.001) but no relation to stroke volume or aortic velocity. Variability of intra-animal and intragroup parameter estimation were frequently 2-fold larger for ketamine/xylazine anesthesia vs. halothane. Statistical power analysis showed the increased measurement error for ketamine/xylazine leads to much larger numbers of mice/group to achieve identical statistical sensitivity. These data further illustrate the feasibility of echocardiography for rapid, non-invasive cardiovascular assessment in mice. However, several obtainable parameters are highly sensitive to both heart rate and anesthetic used and the choice and control of anesthetic are critical for physiologically relevant performance parameters and maximal ability to detect statistical differences among groups. Thus, for these non-invasive studies, inhalation anesthesia with agents such as halothane is superior to anesthesia induced by ketamine/xylazine administration.     

Dilatory and inotropic effects of corticotropin-releasing factor (CRF) on the isolated heart. Effects on atrial natriuretic peptide (ANP) release.

The effects of CRF administration on cardiac performance, coronary flow and ANP release were investigated in the rat heart. Isolated hearts were perfused at a constant filling pressure according to working heart model with a Krebs-Henseleit solution containing glucose and insulin, saturated with a gas mixture containing 95% O2 and 5% CO2. Administration of CRF via a cannula into the left atrium elicited a prolonged increase in the coronary flow rate and a transient increase in the aortic pressure resulting in an overall increase in the pressure-volume work. The oxygen consumption, after the administration of CRF, increased in accordance with the cardiac effort. No changes were observed in the spontaneous heart rate. Furthermore, administration of CRF induced a short-term increase of ANP release into the coronary perfusate. Our experiments suggest that administration of CRF produces a prolonged dilatory effect on the coronary arteries while producing a transient positive inotropic effect and a transient increase of ANP release on the isolated rat heart.     

Ghrelin,a novel growth hormone-releasing peptide,in the treatment of chronic heart failure

Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which has been identified as an endogenous ligand for growth-hormone secretagogues receptor (GHS-R). This peptide also causes a positive energy balance by stimulating food intake and inducing adiposity through growth hormone-independent mechanisms. In addition, ghrelin has some cardiovascular effects, as indicated by the presence of its receptor in blood vessels and the cardiac ventricles. In vitro, ghrelin inhibits apoptosis of cardiomyocytes and endothelial cells. In humans, infusion of ghrelin decreases systemic vascular resistance and increases cardiac output in patients with heart failure. Repeated administration of ghrelin improves cardiac structure and function and attenuates the development of cardiac cachexia in rats with heart failure. These results suggest that ghrelin has cardiovascular effects and regulates energy metabolism through GH-dependent and -independent mechanisms. Thus, administration of ghrelin may be a new therapeutic strategy for the treatment of severe chronic heart failure (CHF).     

心力衰竭大鼠心肌SERCA2a和miR-25-3p/5p表达的改变及泻肺利水方药的干预作用

目的：观察心力衰竭大鼠肌浆网钙ATP酶（SERCA2a） mRNA和miR-25-3p/5p表达水平的变化及中药泻肺利水方药的干预作用。方法：SD大鼠随机分为对照组、模型组、中药组、卡托普利组和地高辛组（n=10）,阿霉素腹腔注射（总剂量15 ml/kg,2周内分6次注射）建立心力衰竭大鼠模型,5周后分别以蒸馏水（10 ml/（kg·d））、泻肺利水中药（22 g/（kg·d））、卡托普利（19 mg/（kg·d））和地高辛（32μg/（kg·d））连续灌胃35 d,观察大鼠心肌SERCA2amRNA、miR-25-3p/5p的表达水平和SERCA2a活性、血浆脑钠肽水平、心输出量和射血分数。结果：模型组大鼠心输出量和射血分数显著降低,心肌SERCA2a mRNA表达水平和活性降低,miR-25-3p和miR-25-5p的表达水平、血浆脑钠肽水平显著升高;泻肺利水中药能提高心肌SERCA2a mRNA表达水平和活性,降低miR-25-3p和miR-25-5p的表达水平,降低血浆脑钠肽水平,提高心输出量和射血分数;卡托普利能提高心肌SERCA2a mRNA表达水平,降低miR-25-3p和miR-25-5p的表达水平,降低血浆脑钠肽水平,提高心输出量;地高辛能提高心肌SERCA2a mRNA表达水平,降低血清脑钠肽水平,提高心输出量。结论：心力衰竭大鼠心肌SERCA2a mRNA的表达下调,miR-25-3p和miR-25-5p的表达上调;泻肺利水方药可以上调SERCA2a mRNA的表达,下调心肌miR-25-3p和miR-25-5p的表达,改善心功能。