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Dobutamine stress cine-MRI of cardiac function in the hearts of adult cardiomyocyte-specific VEGF knockout mice.

A mouse model of non-necrotic vascular deficiency in the adult heart was studied using cine-magnetic resonance imaging (MRI) and other techniques. The mice lacked cardiomyocyte-derived vascular endothelial growth factor (VEGF) following a targeted knockout in the ventricular cardiomyocytes. Quantitative endothelial labeling showed that the capillary density was significantly reduced in the hearts of knockout mice. Gene expression patterns suggested that they were hypoxic. Semiautomated MR image analysis was employed to obtain both global and regional measurements of left ventricular function at 10 or more time points through the cardiac cycle. MRI measurements showed a marked reduction in ejection fraction both at rest and under low- and high-dose dobutamine stress. Regional wall thickness, thickening, and displacement were all attenuated in the knockout mice. A prolonged high-dose dobutamine challenge was monitored by MRI. A maximal response was sustained for 90 minutes, suggesting that it did not depend on endogenous glycogen stores.

Animals↗

Cardiac function, metabolism and perfusion in Duchenne and Becker muscular dystrophy.

We studied 23 DMD and eight BMD patients using cardiac echo, 24 h ECG and positron emission tomography (PET) with the radiotracers N-13 ammonia and F-18 fluorine deoxyglucose. The ECG was abnormal in 23 cases with alterations in the PR and/or QT intervals, abnormal Q waves in the lateral leads and ST segment depression. Twenty-four hour ECG showed that patients were more likely to produce premature ventricular ectopic beats with advancing age and 17 patients had paroxysmal ST segment depression. LV function was normal or mildly reduced in 24 cardiac echoes. PET studies were visibly abnormal in 15 patients. Regional perfusion defects involving the apex, lateral or anterior left ventricular walls were present, nine cases demonstrated a corresponding increase in glucose metabolism. Three out of 15 demonstrated matched perfusion/metabolism defects. One BMD had severe LV dilation with globally poor perfusion and metabolism. The abnormalities seen with PET were confirmed with both quantitative and semi-quantitative analysis of radioactive counts. Similar results were obtained for both DMD and BMD, where both groups demonstrated significant regional perfusion/metabolism mismatches. We have shown a reduced uptake of N-13 ammonia which is indicative of a reduction in myocardial perfusion. The use of N-13 ammonia to measure perfusion has been validated in animal studies. PET with either N-13 ammonia- or oxygen labelled water can be used to measure myocardial perfusion. We chose N-13 ammonia as this was most readily available to us.

Adolescent↗

Effects of nitroprusside on cardiac function, blood flow distribution, and oxygen consumption in the conscious young lamb.

Resting cardiac output is high relative to body weight during the neonatal period and there is a limited reserve for further increasing cardiac output. We assessed the effect on the circulation of reducing peripheral vascular resistance by infusing high doses of sodium nitroprusside in 1- and 3-week-old lambs. In a dose of 5 micrograms X kg-1 X min-1 over 1 h, nitroprusside caused a decrease in aortic and left atrial pressure, an increase in heart rate, and no significant changes in cardiac output or oxygen consumption. Infusing 10 micrograms X kg-1 X min-1 for 2 h resulted in an initial marked decrease in aortic pressure, cardiac output, and also heart rate. Within 50 min aortic pressure gradually increased, but was still well below control levels, while cardiac output returned to control level and heart rate slowly increased. Distribution of cardiac output and organ blood flows was measured by the radionuclide microsphere method. Blood flows to the kidneys and to the skin fell markedly, but flows to other organs did not change significantly.

Aging↗

Adenosine receptor-mediated alterations in prostacyclin production and cardiac function in the isolated rabbit heart.

The subtype of adenosine receptor linked to cardiac prostacyclin (PGI2) synthesis, measured as immunoreactive 6-keto-PGF1 alpha, was investigated in the rabbit heart perfused with Krebs' buffer at 20 ml/min. Adenosine (6.4-50 nmol) decreased 6-keto-PGF1 alpha synthesis, coronary perfusion pressure (PP) and myocardial contractility (dp/dt max), whereas higher doses (200 nmol) increased 6-keto-PGF1 alpha output and decreased PP, heart rate (HR) and dp/dt max. Injections (3.2-50 nmol) or infusion (0.6 microM) of A1 receptor agonist 1-deaza,2-chloro,N6 cyclopentyladenosine increased 6-keto-PGF1 alpha production and decreased HR and PP without affecting dp/dt max. 1-Deaza,2-chloro,N6 cyclopentyladenosine 100 to 200 nmol produced similar effects as lower doses except that it decreased transiently PP and reduced dp/dt max. 1,3-Dipropyl,8-cyclopentylxanthine (0.06 microM) prevented the effects of 1-deaza,2-chloro,N6 cyclopentyladenosine (50 mumol) and adenosine (10 microM) to increase 6-keto-PGF1 alpha output and decrease HR and minimized the decrease in dp/dt max. A2 receptor agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido-ade nos ine (1.6-12.5 nmol) or 0.6 microM decreased 6-keto-PGF1 alpha output, PP and dp/dt max without changes in HR. 3,7-Dimethyl-1-propargylxanthine prevented 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine-induced decrease in 6-keto-PGF1 alpha output, PP and dp/dt max; HR was not altered by this agent. These data suggest that stimulation of A2 receptors reduce cardiac PGI2 synthesis and PP, but activation of A1 adenosine receptors increased PGI2 synthesis, produced vasoconstriction and decreased HR.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

High-frequency jet ventilation improves cardiac function after the Fontan procedure.

Pulmonary vascular resistance is an important determinant of cardiac output after the Fontan procedure and is adversely affected by elevated mean airway pressure. High-frequency jet ventilation (HFJV) is an alternate form of mechanical ventilation which supports gas exchange at lower mean airway pressure. This study was performed to determine if HFJV could lower mean airway pressure and pulmonary vascular resistance and result in an increase in cardiac output after the Fontan procedure. We prospectively evaluated 13 patients ranging in age from 0.9 to 8.5 years (mean, 3.9 years) and in weight from 6.2 to 20.1 kg (mean, 13.9 kg). Right atrial, left atrial and pulmonary artery catheters were used to measure hemodynamic parameters. Cardiac index was measured by dye dilution technique, and pulmonary vascular resistance was calculated. The patients were stabilized on mechanical ventilation to achieve a PaCO2 = 30 +/- 5 mm Hg, and baseline hemodynamic and respiratory measurements were made. HFJV was begun at settings adjusted to achieve similar gas exchange. Respiratory and hemodynamic measurements were repeated after 30-60 minutes of HFJV. Mechanical ventilation was then resumed at baseline settings, and measurements were repeated 0.5-1 hour later. There was no significant change in gas exchange. HFJV resulted in a 50% reduction in mean airway pressure (9.2 +/- 0.2 cm H2O to 4.6 +/- 0.1 cm H2O, p less than 0.001), a 59% reduction in pulmonary vascular resistance (3.82 +/- 0.36 to 1.52 +/- 0.16 Woods units, p less than 0.001), and a 25% increase in cardiac index (2.32 +/- 0.12 l/min/m2 to 2.91 +/- 0.12 l/min/m2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Effects of nipradilol (K-351) on cardiac function in anesthetized open-chest dogs.

Effects of nipradilol (K-351) on cardiac performance and myocardial oxygen consumption were investigated in anesthetized open-chest dogs. Nipradilol 0.1 mg/kg i.v. induced falls in systolic and diastolic aortic blood pressure and left ventricular pressure, and decreases in cardiac output, coronary sinus outflow, left ventricular dP/dt and heart rate. Stroke volume was transiently increased and left ventricular stroke work index was significantly decreased, while left ventricular mechanical efficiency was not significantly changed. Myocardial oxygen consumption was significantly decreased. Total peripheral vascular resistance and coronary vascular resistance were persistently increased. Left ventricular enddiastolic pressure was not significantly changed. These results suggest that nipradilol has a possible antianginal property through a decrease in myocardial oxygen consumption due to a fall in aortic blood pressure and a decrease in heart rate.

Adrenergic alpha-Antagonists↗

Abnormal cardiac function after exercise in insulin-dependent diabetic children and adolescents.

We evaluated the cardiac response to dynamic exercise in a group of otherwise healthy insulin-dependent older children and adolescents and in a nondiabetic control group by postexercise echocardiography. Both groups had similar left ventricular function at rest. After exercise we found abnormalities in the indicators of systolic function, fractional shortening (0.37 vs. 0.43) and rate-corrected velocity of circumferential fiber shortening (2.80 vs. 3.35 circumferences/s). In addition, we found an association of flattened interventricular septal motion with finger contractures in the diabetic subjects. Echocardiographic abnormalities in asymptomatic young diabetic adolescents can be elucidated by postexercise echocardiography. Postexercise echocardiography is a noninvasive procedure that can easily be done in the adolescent population and is useful for evaluating subclinical cardiomyopathy.

Adolescent↗

Left ventricular systolic and diastolic function, and exercise capacity six to eight weeks after acute myocardial infarction. The DEFIANT Study Group. Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy.

Echocardiographic and Doppler-derived measurements of left ventricular (LV) function at rest were examined as predictors of maximal bicycle exercise capacity in a homogeneous group of 115 patients with mild to moderate LV dysfunction (ejection fraction 22 to 56%, median 43%) participating in the DEFIANT study of nisoldipine after acute myocardial infarction. Although the relations were not exact, peak exercise work load 7 weeks after infarction correlated with measurements of diastolic LV function at rest. Exercise work load was inversely related to peak late diastolic transmitral blood flow velocity (A wave) (slope -86.6; 95% confidence interval -120.9 to -52.2) and directly to the E/A ratio (slope 20.5; 95% confidence interval 6.0 to 35.1). The relations between exercise work load and peak late diastolic flow velocity remained significant after correction for age, sex, heart rate at rest, and use of beta-blocking drugs or nisoldipine. There was no relation between peak exercise work load and peak early diastolic transmitral flow velocity (E wave), isovolumic relaxation period or deceleration time. Measurements of systolic LV function (LV end-diastolic and end-systolic volumes, and ejection fraction, stroke volume and cardiac index) were also not significant as predictors of exercise capacity.

Adult↗

Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor.

Transgenic mice were created with cardiac-specific overexpression of the beta-adrenergic receptor kinase-1 (beta ARK1) or a beta ARK inhibitor. Animals overexpressing beta ARK1 demonstrated attenuation of isoproterenol-stimulated left ventricular contractility in vivo, dampening of myocardial adenylyl cyclase activity, and reduced functional coupling of beta-adrenergic receptors. Conversely, mice expressing the beta ARK inhibitor displayed enhanced cardiac contractility in vivo with or without isoproterenol. These animals demonstrate the important role of beta ARK in modulating in vivo myocardial function. Because increased amounts of beta ARK1 and diminished cardiac beta-adrenergic responsiveness characterize heart failure, these animals may provide experimental models to study the role of beta ARK in heart disease.

Adenylyl Cyclases↗

Real-time ventricular volumes and cardiac function in the working rat heart.

The measurement of instantaneous left ventricular volumes throughout the cardiac cycle in a rat heart beating at rates of 300 to 600 min-1 with a chamber volume of only a few tenths of a milliliter is difficult. Combining an x-ray scatter detection system with a small x-ray source collimated to scatter low energy x-rays off a working rat heart, measurements of real-time changes in ventricular volumes can be determined. The x-ray scatter signal is proportional to the volume and can be calibrated to measure the actual volume. Using this system, changes in ventricular function can readily be detected. An example of data obtained from increasing preload with a fixed afterload is shown. This technique not only distinguishes an increasing stroke volume, but also more rapid early diastolic filling and systolic ejection rates with increasing preload. This new x-ray scatter technique appears to be a promising way to measure rapidly changing left ventricular volumes and function in the working rat heart. This could significantly enhance the scientific use of the rat model.

Animals↗

Investigation of cardiac function in children with suspected obstructive sleep apnea.

OBJECTIVE: To assess the prevalence of cardiac failure in a group of children with suspected obstructive sleep apnea (OSA) and to assess the need for preoperative electrocardiograms (ECGs) and chest radiographs (CXRs) in children with OSA. DESIGN: Case record review of 271 children having (adeno)tonsillectomy for symptoms of OSA. METHOD: Preoperative ECGs and CXRs were assessed for signs of right atrial or ventricular hypertrophy or failure. Case records were assessed for evidence of cardiac failure during anaesthesia. RESULTS: One child with congenital heart disease had signs of cardiac failure preoperatively. No other cases of atrial or ventricular hypertrophy or failure were found. CONCLUSIONS: Cardiac failure appears to be uncommon in children with symptoms of OSA. Preoperative ECG and CXR are essential in only selected cases.

Adolescent↗

Echocardiographic analysis of cardiac function during high PEEP ventilation.

OBJECTIVE: Does positive end-expiratory pressure ventilation (PEEP) deteriorate cardiac contractility? DESIGN: By means of echocardiography nine piglets were studies during ventilation with 0, 15 and 25 cmH2O (PEEP). Recordings were made before and after 500 ml of 6% dextran 70. MEASUREMENT AND RESULTS: Right and left ventricular end-diastolic diameters were plotted against the stroke volume determined by the thermodilution technique. By combining observations made before and after volume expansion during the different ventilation modes, a ventricular function curve was obtained. The slopes of the curves were similar during all three ventilation modes, both on the left and on the right side. CONCLUSION: This study indicates undisturbed myocardial contractility during PEEP ventilation. We infer that the cardiac output deterioration in the intact animal is caused entirely by impairment of venous return.

Animals↗

Use of a hand-carried ultrasound device by critical care physicians for the diagnosis of pericardial effusions, decreased cardiac function, and left ventricular enlargement in pediatric patients.

Prompt diagnosis of children with suggested cardiac disease in the acute care setting is critical for initiation of life-saving therapy. We hypothesized that pediatric critical care physicians could perform limited portable echocardiography in children. Portable hand-carried cardiac ultrasound units with 2.5-MHz phased-array transducers were used (Optigo, Philips Medical Systems, Andover, Mass). Noncardiologists were trained through a 1-hour introductory course and 2 hours of practical training. Portable echocardiography performed by noncardiologists was compared with a standard echocardiogram for diagnostic accuracy. In all, 23 patients (age 3 months-20 years) were screened during 18 months. The presence or absence of a pericardial effusion was correctly diagnosed in 21 of 23 patients (91%). Left ventricular size was correctly determined in 22 of 23 patients (96%). Left ventricular systolic function was correctly diagnosed in 22 of 23 patients (96%). These results show that, with appropriate instruction, pediatric critical care physicians are effective using limited portable echocardiography.

Adolescent↗