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Resuscitation with hypertonic saline dextran improves cardiac function in vivo and ex vivo after burn injury in sheep.

In a 24 h, double-blind, prospective trial, we tested the hypothesis that two 4 mL/kg doses of hypertonic saline dextran (HSD; 7.5% NaCl/6% dextran 70) given in addition to isotonic fluid treatment would produce both immediate and sustained benefit for the heart after large burn injury. 12 instrumented sheep were subjected to a 40% total body surface area full-thickness flame burn under halothane anesthesia. 1 h after burn, when the animals had recovered from anesthesia, the first dose of either HSD (n=6) or normal saline (NaCl .9%; n=6) was infused over 30 min. The test solution was immediately followed by lactated Ringer's solution infused to maintain a urine output of 1-2 mL/kg x h throughout the study. The second dose of test solution was started at 12 h and was infused over 5 h. The initial dose of HSD corrected the burn-induced reduction in cardiac output, cardiac work, an index of myocardial contractility, and restored myocardial blood flow, as measured by the colored microsphere technique, to preburn values. Plasma concentrations of troponin I, creatine kinase (CK), and CK isoenzyme CKMB were increased 1 h after burn, but were not altered after HSD treatment. After euthanasia at 24 h, myocardial glutathione concentrations were higher in HSD-treated animals, whereas other markers of oxidative injury in heart or in plasma did not show systematic differences. The maximum contraction force measured in isolated right papillary muscles ex vivo was significantly greater in HSD-treated than normal saline-treated animals. In conclusion, the first dose of 4 mL/kg HSD infused 1 h after burn improved cardiac function, whereas the second dose of HSD infused at 12 h was without apparent effect on dynamic variables. An overall effect of the HSD treatments was a lasting increase in papillary muscle contraction force.

Animals↗

Cardiac function of transplanted rat hearts using a working heart model assessed by magnetic resonance imaging.

BACKGROUND: A direct correlation between graft rejection and cardiac contractile function in small-animal models has been difficult to establish because (i) the conventional non-working heart model is greatly different from the orthotopic heart in terms of left ventricular work and (ii) it is difficult to obtain hemodynamic data in situ. We have used magnetic resonance imaging (MRI) techniques to obtain noninvasive, in-situ quantitation of ventricular volume after heterotopic cardiac transplantation. METHODS: Infra-renal heterotopic cardiac transplantation was performed on rats using syngeneic and allogeneic untreated donors in both working and non-working left heart models. An occluding balloon catheter in the inferior vena cava was used to vary the pre-load to the graft. An arteriovenous fistula was created to raise inferior caval oxygen saturation. Magnetic resonance imaging measurements were carried out at day 3, 4, and 5 post-transplantation. Left ventricle end-diastolic and end-systolic volumes were calculated using a biplanar ellipsoid model. RESULTS: Stroke volume was significantly increased in the working heart model as compared to the non-working model. At day 4 post-transplant, the diastolic pressure-volume relationship in the allograft group was significantly shifted, indicative of decreased myocardial distensibility, whereas the indices of systolic function were preserved. CONCLUSIONS: We have developed a heterotopic transplant working rat heart model and have used it to assess in-situ cardiac function by MRI. Sensitive indices of diastolic contractile function can be obtained in this rodent transplant model that correlate well with histologic evidence of early rejection.

Animals↗

H2S generated by heart in rat and its effects on cardiac function.

Hydrogen sulfide (H2S), which was considered as a novel gasotransmitter, is produced endogenously from L-cysteine in mammalian brain and vessels, and might be a physiological function regulator to these organs. Here, we showed that mRNA for H2S producing enzyme, cystathionine gamma-lyase, was expressed in myocardial tissues and H2S could endogenously be produced in myocardial tissues. Negative inotropic effect of H2S was proved in present study in vitro and in vivo experiments, and the effect could partly be blocked by glibenclamide, a KATP channel blocker. An intravenous bolus injection of NaHS provoked a decrease in central venous pressure. The present findings suggested that H2S could be endogenously produced by heart tissues, as a physiological cardiac function regulator, mediated by KATP channel pathway.

Animals↗

[Semi-invasive measurement of pulmonary pressure as a method of evaluating cardiac function in hypertension and ischemic heart disease. Experience at Charité Hospital for more than 20 years].

Since 1969, microcatheterization (floating catheterization) of the pulmonary artery has systematically been used at the Hospital Charité in Berlin for measuring (indirectly) the left ventricular filling pressure. That seemed especially be justified in patients in whom conventional catheterization was not needed. Noninvasive techniques had not been available. Since then, our interest was focused on the hypertensive heart, earlier under the aspect of early discovering and influencing heart insufficiency, later concerning a developing myocardial ischemia, in relationship to left ventricular hypertrophy. At the Charité more than 1,000 microcatheterizations in more than 400 hypertensive cases have been performed, mostly in combination with nuclear-cardiological measurements. The rate of complications was found minimal. Thus, cardiac function could be characterized hemodynamically, at rest and even under ergometric load. Special programmes served the acute application of drugs for diagnostic or therapeutic reasons. In the meantime a longterm study could also be finished by using hemodynamic measurements, starting with hygienic means and followed by a antihypertensive basis therapy, in newly detected hypertensives. That included repeated catheterizations of the pulmonary artery.

Catheterization, Peripheral↗

Carvedilol improved diabetic rat cardiac function depending on antioxidant ability.

The risk for cardiovascular disease is significantly high in diabetes mellitus. Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has a close connection with antagonizing oxidative stress destroy in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant and free radical scavenger properties. To study the effect of carvedilol on the antioxidant status and expression of Bcl-2 in healthy and diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage (1 or 10mg/kg/d) carvedilol-administrated for 5 weeks, hemodynamic parameters, the levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and expression of Bcl-2 mRNA in the cardiac tissues of all six groups were measured. Diabetic rats had higher left ventricular end diastolic pressure (LVEDP), lower maximal rate of rise/fall left ventricle pressure development and decline (+/-dP/dtmax). These parameters were improved by administration of carvedilol. Diabetic rats showed elevated MDA level and CAT activity, but lower activities of SOD and GSH-Px. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicate that carvedilol improves cardiac function via its antioxidant property in diabetic rats partly.

Animals↗

Therapeutic effects of an androgenic preparation on myocardial ischemia and cardiac function in 62 elderly male coronary heart disease patients.

The elevated estradiol/testosterone (E2/T) ratio had been proved to be a risk factor for coronary heart disease (CHD) in elderly men. We conducted a randomized placebo controlled crossover study on the effects of a new androgenic preparation "Andriol" in 62 elderly men with CHD over a period of 2.5 months. The results showed significant differences between Andriol- and placebo-treated groups at the end of this period: in the former, serum T level was elevated significantly (P < 0.001), E2 level was unchanged (P > 0.05), E2/T ratio was reduced (P < 0.05), angina pectoris (AP) was relieved (total effective rate, 77.4%), and myocardial ischemia in ECG and Holter recordings were improved (total effective rate, respectively 68.8% and 75%). Doppler echocardiography showed that 12 parameters of cardiac function were unchanged in both groups. No obvious side effect was found in those who took Andriol.

Aged↗

Maternal cardiac function in fetal growth restriction.

OBJECTIVE: To assess the maternal central haemodynamics in normotensive women with pregnancies complicated by severe fetal growth restriction (FGR). DESIGN: Cross-sectional study. SETTING: A tertiary referral fetal medicine unit. POPULATION: The study groups comprised 107 women with normal singleton pregnancies and 20 with singleton pregnancies complicated by FGR at 25-37 weeks. In the latter group, assessment was carried out within 10 days prior to their delivery. All the women were normotensive, without any medical problems. METHODS: Two-dimensional and M-mode echocardiography of the left ventricle. MAIN OUTCOME MEASURES: Maternal left ventricular systolic and diastolic function. RESULTS: In the FGR group, compared with the normal group, there was increased total vascular resistance (TVR), reduced systolic function characterised by lower cardiac output, stroke volume, heart rate, ejection time and septal and lateral long-axis shortening. Mean arterial pressure (MAP) was not significantly different between the groups. CONCLUSIONS: Severe FGR is associated with reduced maternal systolic function and increased TVR but no change in MAP. TVR may be a useful tool in the classification and management of FGR. The findings suggest that in FGR, there is increased blood viscosity due to lack of intravascular space expansion.

Adult↗

Hypothesis: Correction of low vitamin D status among Arab women will prevent heart failure and improve cardiac function in established heart failure.

Vitamin D deficiency is common in Arab countries particularly among women. This is the result of a low dietary intake of the vitamin, limited exposure to sunlight (a paradox in view of the high sunshine figures), skin colour, obesity and high parity. Apart from its adverse effects on bone in women and their offspring, vitamin D deficiency has the potential to cause or exacerbate heart failure through a number of mechanisms including activation of the renin-angiotensin system and increased arterial pressure. Accordingly, we propose that ensuring adequate vitamin D levels in Arab women will have a much greater impact on health than just the prevention of bone disease. In particular, we suggest that prevention and correction of vitamin D deficiency will reduce the incidence of heart failure and, for Arab women with established heart failure and vitamin D deficiency, improve cardiac function.

Arabs↗

Prognostic evaluation of congestive heart failure in patients with Duchenne muscular dystrophy--retrospective study using non-invasive cardiac function tests.

The relation between heart function and the prognosis of patients with Duchenne muscular dystrophy (DMD) was analyzed in 27 non-survivors and 40 survivors by fractional shortening (FS) of the left ventricle from M-mode echocardiogram, and by the PEP/ET ratio from the systolic time interval. The patients were divided into 5 groups; (1) patients who died of congestive heart failure (group 1), (2) those who died of congestive heart failure and respiratory failure (group 2), (3) those who died of respiratory failure (group 3), (4) those who died suddenly of undefined etiology (group 4), and (5) survivors (group 5). Data from non-invasive cardiac function tests were analyzed retrospectively for 2 years and compared at 2 years, 1 year and about 3 months before their deaths in cases of group 1, 2, 3 and 4, and the data obtained at the same period were also compared with those of survivors (group 5). The age at death in group 1 (17.3 +/- 4.9 years) was significantly younger than that in group 2 (25.3 +/- 4.2 years), however, it did not statistically differ from group 3 (19.8 +/- 3.3 years old). The values of FS in group 1 were significantly lower than those in group 3, 4 and 5 at three examinations, whereas no difference in PEP/ET was observed among them. Cardiothoracic ratio (CTR) on chest X-ray in group 1 was not significantly different from other groups in each period, but the left ventricle dilated rapidly in the terminal stage of congestive heart failure which could be more precisely detected by the M-mode echocardiogram. These results indicate that in DMD, early development of congestive heart failure was associated with a poor prognosis. FS was a most sensitive non-invasive tool in predicting the prognosis. A significant reduction in FS was detectable 2 years before death. Progression in abnormality of left ventricular dimension as well as in FS may be another useful index for evaluating the prognosis of patients dying from congestive heart failure.

Adolescent↗

[Effects of components isolated from Astragalus membranaceus Bunge on cardiac function injured by myocardial ischemia reperfusion in rats].

OBJECTIVE: To investigate the effects of components isolated from Astragalus membranaceus on myocardial ischemia reperfusion injury. METHODS: The myocardial ischemia reperfusion injury model was created by the left anterior descending coronary artery occlusion from the oracotouated rats, and the total saponins, total flavonids and astragaloside i.v. isolated from A. membranaceus on hemodynamics during acute myocardial ischemia, Na(+)-K(+)-ATPase activity, cAMP and malondialdehyede (MDA) contents in the ischemic myocardium were observed. RESULTS: The total saponins, total flavonids and astragaloside i.v. attenuated the declines of the amplitudes of LVSP and +/- LVdp/dtmax in rat heart injured by ischemia reperfusion in vivo, and decreased Na(+)-K(+)-ATPase activity in the ischemic myocardium. Otherwise, the total saponins increased the cAMP content and the total flavonids decreased the level of MDA production in the ischemic myocardium. CONCLUSION: The effects of different components isolated from A. membranaceus on protecting the cardiac function in the process of ischemia reperfusion may be related to the mechanism of improving energy metabolism, scavenging the oxygen free radicals and inhibiting the production of free radicals in the ischemic myocardium.

Animals↗

Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion.

The p53-upregulated modulator of apoptosis (Puma), a BH3-only member of the Bcl-2 protein family, is required for p53-dependent and -independent forms of apoptosis and has been implicated in the pathomechanism of several diseases, including cancer, acquired immunodeficiency syndrome, and ischemic brain disease. The role of Puma in cardiomyocyte death, however, has not been analyzed. On the basis of the ability of Puma to integrate diverse cell death stimuli, we hypothesized that Puma might be critical for cardiomyocyte death upon ischemia-reperfusion (I/R) of the heart. Here we show that hypoxia-reoxygenation of isolated cardiomyocytes led to an increase in Puma mRNA and protein levels. Moreover, if Puma was delivered by an adenoviral construct, cardiomyocytes died by apoptosis. Under ATP-depleted conditions, however, Puma overexpression primarily induced necrosis, suggesting that Puma is involved in the development of both types of cell death. Consistent with these findings, targeted deletion of Puma in a mouse model attenuated both apoptosis and necrosis. When the Langendorff ex vivo I/R model was used, infarcts were approximately 50% smaller in Puma(-/-) than in wild-type mice. As a result, after I/R, cardiac function was significantly better preserved in Puma(-/-) mice than in their wild-type littermates. Our study thus establishes Puma as an essential mediator of cardiomyocyte death upon I/R injury and offers a novel therapeutic target to limit cell loss in ischemic heart disease.

Animals↗

Adenosine A1 and A2 receptor agonists alter cardiac functions and prostacyclin release in the isolated guinea-pig heart.

The actions of the adenosine A1 receptor agonist CCPA (2-chloro-N6-cyclopentyladenosine) and the adenosine A2 receptor agonist CGS 21680 (2-[p-(2-carboxyethyl(phenethylamino]-5'-N- ethylcarboxamidoadenosine) on myocardial functions and prostacyclin release were studied in Langendorff-perfused guinea-pig hearts. In spontaneously beating hearts, perfused at constant pressure, CCPA reduced heart rate and left ventricular actively developed pressure with EC50 values of 54.4 +/- 8.7 nM and 81 +/- 6.2 nM, respectively. The adenosine A1 receptor antagonist PACPX (1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine, 1 microM) antagonized the effects of CCPA on heart rate and left ventricular actively developed pressure and increased the EC50 values 11-fold and 8-fold, respectively. CGS 21680 caused vasodilatation and doubled the coronary flow rate (EC50 of 5.77 +/- 3 nM). The potent but non-selective adenosine receptor antagonist CGS 15943A (9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo(1,5-c)quinazolin++ +-5-imine, 0.1 microM) caused a shift to the right of the concentration-response curve of CGS 21680 for coronary flow rate and increased the EC50 value 52-fold. In electrically paced hearts, perfused at constant flow rate, CCPA (1-100 nM) and CGS 21680 (10-1000 nM) increased the 6-oxo-prostaglandin F1 alpha release (stable non-enzymatic hydrolysis product of prostacyclin) into the cardiac effluent to a maximum of 170 +/- 16% and 184 +/- 6%, respectively. The effects of CCPA and CGS 21680 on cardiac functions indicate a high selectivity of both agonists for adenosine A1 and A2 receptor subtypes of the isolated guinea-pig heart, respectively. The elevation of 6-oxo-prostaglandin F1 alpha in the effluent of guinea-pig hearts by CCPA and CGS 21680 is possibly independent of stimulation of adenosine receptors on the vascular endothelium.

6-Ketoprostaglandin F1 alpha↗

Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure.

The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.

Animals↗

[Effects of antihypertensive factor on cardiac function in spontaneously hypertensive rats].

In this study, we observed the effects of erythrocytic AHF from normotensive human subjects on heart function of stroke prone SHR (SHRsp) in order to investigate the antihypertensive mechanism of AHF. The results showed that AHF significantly decreased the heart rate (HR), left ventricular end systolic pressure (LVESP), and magnitude of +/- LVdP/dtmax, but had no effect on Wistar Kyoto (WKY) rats, indicating that AHF has negative chronotropic and inotropic action on SHRsp hearts. AHF also lowered the contraction amplitude and resting tension in isolated SHRsp hearts, but had no effect on HR and blood flow of the coronary artery, indicating that AHF exerts negative inotropic action on isolated SHRsp hearts. The results suggest that the antihypertensive mechanism of AHF may be related to its ability to decrease cardiac function in hypertensive rats.

Animals↗

Changes in cardiac function during and after pregnancy expressed by systolic time intervals.

Hemodynamic changes during the first and third trimester in pregnancy and in the first week of puerperium were evaluated by non-invasive measurements of Systolic Time Intervals (STI) in supine and left lateral position. The Pre-ejection Period (PEP) was found to shorten significantly in pregnancy and the puerperium due to the increased blood volume. The electro-mechanical systole (QS2) and left ventricular ejection time (LVET) were shortened too, while PEP/LVET-ratio was increased in the third trimester due to the mechanical compression of the gravid uterus on the inferior vena cava. A lengthening of QS2 and LVET and a decreased PEP and P/L-ratio were demonstrated in the third trimester in lateral position when the pressure of the enlarged uterus was eliminated. Heart rate (HR) increased in late pregnancy as well as after delivery, while arterial blood pressure (BP) only underwent minor changes. Employment of the STI seems to provide more useful information about the changes cardiac function during gestation than HR and BP does. The measurements of STI can be repeated without any risk or inconvenience to the patients.

Adult↗

Left ventricular mass and cardiac function in patients with essential hypertension.

Two-dimensional guided M-mode echocardiography was used to estimate left ventricular mass and left ventricular performance in 140 untreated hypertensive patients, 38 (27%) of whom had left ventricular hypertrophy. Left ventricular contractility as reflected by ratio of end-systolic wall stress to end-systolic volume index and normalised early left ventricular peak filling rate were decreased in the patients with left ventricular hypertrophy compared with those without hypertrophy and correlated inversely with the left ventricular mass (r = -0.44; P < 0.0001 and r = -0.31; P = 0.0004, respectively). Positive correlations were found between the peak filling rate and either the ejection fraction or the contractility index (r = 0.44; P < 0.0001 and r = 0.24; P = 0.004, respectively). Left ventricular mass also correlated with mean arterial pressure in the whole study population (r = 0.43; P < 0.0001). The data suggest that with the development of left ventricular hypertrophy both contractility and filling of the left ventricle become progressively impaired in hypertensive patients. The decline in cardiac function with progressive left ventricular hypertrophy may represent a pathophysiological correlate of the epidemiological observation identifying left ventricular hypertrophy as one of the most powerful risk factors for future cardiovascular morbidity and mortality. The present study shows that with development of left ventricular hypertrophy in essential hypertension both contractility and filling of the left ventricle become progressively impaired.

Adolescent↗

Comparison of treatment effects of bevantolol and metoprolol on cardiac function and natriuretic peptides in patients with dilated cardiomyopathy.

This study was designed to compare the efficacy of bevantolol, a beta(1)-selective blocker with alpha-blockade and vasodilating activity, with that of metoprolol, a beta(1)-selective receptor blocker, for the treatment of idiopathic dilated cardiomyopathy (DCM). Forty-one patients with DCM were enrolled to receive either bevantolol or metoprolol in addition to the standard therapy for DCM. They were classified into two groups: 16 patients were treated with bevantolol and 25 were treated with metoprolol. Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured before treatment and after 6 months of treatment. Left ventricular dimension at end-diastole and end-systole was significantly lower and fractional shortening was significantly higher after treatment than before treatment in both groups. The plasma ANP and BNP levels were significantly decreased in both groups. Changes in all variables, except for systolic blood pressure, showed no significant differences between the two groups. In conclusion, bevantolol showed parallel beneficial effects to those of metoprolol on cardiac function and natriuretic peptides in patients with DCM.

Adrenergic beta-Antagonists↗

Doppler flowmeter-assessed circadian rhythms in neonatal cardiac function, family history, and intrauterine growth retardation.

This study examines the circadian variation of aortic blood flow velocity, acceleration, and distance of stroke, assessed every 4 hours for 24 hours by Doppler ultrasound in 88 human newborns. Groups 1 and 2 involve neonates with a negative family history of high blood pressure or myocardial infarction monitored during the first day or between the second and tenth days postpartum, respectively; groups 3 to 6 are 2- to 10-day-old babies with a positive family history of high blood pressure (group 3) or of myocardial infarction (group 4) or with a negative family history and intrauterine growth retardation (group 5) or born prematurely (group 6). Cosinor analyses demonstrate a circadian rhythm for all variables in groups 2 and 5 (p < 0.001), with overall high values occurring around 17:40. In group 2, a circadian rhythm remains demonstrable in boys and girls considered separately, and mostly so in arbitrary subgroups of different sizes, with only slight differences in rhythm parameters among them. These results show that, with relatively small samples, reproducible circadian rhythms of cardiac function can be detected shortly after birth in neonates with a negative family history of high blood pressure or myocardial infarction.

Analysis of Variance↗