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Regulation of cardiac function in prepubertal rats.

Prepubertal period in rats is characterized by some peculiarities of the cardiac regulatory mechanisms. In 6-week-old rats atropine produced bradycardia instead of tachycardia. Similar reaction was not observed in chemically sympathectomized age-matched rats.

Adrenergic beta-Antagonists↗

Cardiac function in thyroid disease: clinical features and management considerations.

Thyroid disease is often manifested by cardiac abnormalities. The site of the cardiac actions of thyroid hormone, whether from a direct, nuclear effect or an extranuclear effect, remains to be established. Nuclear effects are delayed 1/2 to 1 hour after administration of thyroid hormone, require ongoing protein synthesis, and are thought to result from the binding of thyroid hormone to two separate isoforms of the nuclear thyroid hormone receptor. This binding, which is specific to thyroid hormone response elements, stimulates transcription and results in translation of specific enzymes or contractile proteins. Extranuclear effects may influence plasma membrane transport of calcium, sugar, and amino acids in addition to directly influencing mitochondria and are very rapid, occurring within minutes. It is possible that there exists an interaction between the adrenergic system and the thyroid hormone system, which may also contribute to the cardiac actions of thyroid hormone. This review highlights the clinical manifestations of thyroid disease and the mechanisms of thyroid hormone involved in the cardiac abnormalities.

Heart↗

[Sex and age differences in the effect of verapamil on rat cardiac function].

The author reports that a relatively high dose of verapamil produces sex-related cardiac effects, especially on the conducting system in adult rats. A single dose of verapamil (0.5-1 mg/kg, i.v.) caused a marked AV block and a reduction in heart rate to 50-60% in adult males, but not in females. There was no sex difference in the hypotensive effect of verapamil. At 3, 5 or 7 weeks of age, verapamil (1 mg/kg, i.v.) induced a 10-20% reduction of the heart rate without AV block in both male and female rats. In 8-week-old male rats, the reduction in the heart rate became apparent, and AV block appeared following a single i.v. injection of verapamil. The adult pattern in cardiac response to verapamil was observed at 11 weeks of age and afterward. Castration in adult male and female rats resulted in an intermediate pattern of the response to verapamil in intact male and female rats. Acute treatment with testosterone (20 mg/kg, s.c.) in castrated male and female rats induced a decrease in the basal heart rate and increased the cardiac responsiveness to verapamil in castrated female rats. Estradiol-17 beta failed to alter the responsiveness of castrated rats to verapamil. These results suggest that testosterone may play a role in the sex difference of the cardiac responses to verapamil in rats.

Age Factors↗

Deferoxamine fails to improve postischemic cardiac function in hypertrophied hearts.

Myocardial hypertrophy is a well-recognized risk factor in congenital cardiac surgery. Hypertrophied hearts have been demonstrated to have an increased vulnerability to ischemia/reperfusion injury. We studied the effects of the iron chelator and hydroxyl radical scavenger deferoxamine given during early reperfusion in a model of isolated retroperfused rabbit hearts made hypertrophic by aortic banding early in life (1 week of age). The rabbits were studied at 6-8 weeks of age, and the hearts were subjected to 30 minutes of 37 degrees C ischemia followed by 30 minutes of reperfusion. Postischemic recovery of isovolumic developed pressure was measured by using an intracavitary balloon in both the untreated (n = 6) and the deferoxamine-treated (n = 6) groups and compared with normal age-matched controls. Deferoxamine (50 mumol/kg) was given to one group with the hypertrophied hearts during the first 10 minutes of reperfusion. The left ventricular weight/body weight ratio in the hypertrophied hearts was 2.9 +/- 0.4 x 10(-3) (n = 14) versus 2.0 +/- 0.1 x 10(-3) in the age-matched controls (p less than 0.05). Postischemic peak developed pressure recovered to 102 +/- 6% of the preischemic value in the normal hearts after 30 minutes of reperfusion compared with 75 +/- 5% for the untreated and 71 +/- 4% for the deferoxamine-treated hearts (p less than 0.05 vs. control). We conclude that chronic hypertrophy from early in life leads to increased susceptibility to ischemia and that the iron chelator deferoxamine is not effective in preventing the injury of reperfusion in hypertrophied hearts.

Animals↗

Gender and strain variations in left ventricular cardiac function and mass determined with magnetic resonance imaging at 7 tesla in adult mice.

OBJECTIVES: We sought to assess with magnetic resonance imaging (MRI) the influence of strain type and gender on left ventricular (LV) global function and mass in 3 inbred mouse strains with a normal cardiac phenotype. MATERIALS AND METHODS: A total of 30 mice from 3 inbred strains (C57BL/6, 29S2/SvPasCrl, and C3HFeJ) were studied on a 7.05-T MR scanner using ECG-triggered cine sequences. LV mass and volumes were calculated with inclusion and exclusion of papillary muscles (PMs) in the LV wall. RESULTS: Significant differences were found with strain and gender (P < 0.001), with strain-effect but no gender-effect for ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV). There were no differences in LV mass between strains but lower values in female mice except in the C3H strain. The exclusion of PMs led to the relative underestimation of EF (-6.1%) and of LV mass (-6.4 mg) and the relative overestimation of EDV (6.3 microL) and ESV (5.3 microL). Inter- and intraobserver reproducibility was better when PMs were included. CONCLUSION: The use of MRI demonstrates cardiac interstrain and gender-related phenotypic diversities that are essential factors to consider when building genomic databases and designing studies.

Analysis of Variance↗

The effect of mediastinal irradiation on cardiac function of patients treated during childhood and adolescence for Hodgkin's disease.

To determine the frequency of cardiac dysfunction in patients treated during childhood or adolescence with mediastinal irradiation for Hodgkin's disease (HD), 28 patients underwent cardiac evaluation 19 to 182 months (median, 90 months) after the completion of radiation therapy. No patient had symptoms of cardiac disease. All were normotensive. All patients had a normal cardiothoracic ratio. There were no abnormalities of voltage or rhythm in the ECGs. The left ventricular end diastolic volume was increased in 19.2% of patients, none of whom had evidence of impaired left ventricular function. The left ventricular ejection fraction (LVEF) was increased in 15.3% of patients. No patient had a decreased LVEF. Pericardial thickening was demonstrated on echocardiograms from 12 of 28 patients (42.9%). Thickening was more frequent among those patients observed for 72 or more months (47.1%; eight of 17) than among those with shorter periods of follow-up (36.4%; four of 11). This study demonstrates that cardiac dysfunction is an infrequent sequela of mediastinal irradiation following treatment using an equally weighted, anterior-posterior technique. Longitudinal study of these patients will be necessary to determine the clinical significance and evolution of the occult pericardial thickening that was identified.

Adolescent↗

Acute effects of direct cell implantation into the heart: a pressure-volume study to analyze cardiac function.

BACKGROUND: To safely implant cells into the myocardium, we must establish a volume that prevents compromising cardiac performance. We studied pressure-volume (PV) to investigate the adverse effects of direct cell implantation in the acute phase. METHODS: We used 21 minipigs. In the normal heart model, we studied PV by measuring various parameters (including end-systolic pressure, end-systolic elastance, dp/dtmax, end-diastolic volume, and time constant of isovolumetric left ventricular pressure fall [Tau]). We injected solutions into the left ventricular free wall (15 cm(2)). Sampling points were at baseline and after injection of saline (Group I, n = 4) or of blood (Group II, n = 4) at volumes of 1 ml and 10 ml up to 30 minutes after injection. In Group II, we injected additional blood (10 ml) 4 times. In the ischemic heart model, 1 month after ligating the left anterior descending artery, we injected 1 ml saline (Group III, n = 4), bone marrow mononuclear cells (10(8) cells/1 ml; Group IV, n = 4), or bone marrow stromal cells (10(8) cells/1 ml; Group V, n = 3). We studied PV before and after injection. RESULTS: In Group I, we found no significant changes in parameters. In Group II, end-diastolic volume after 10-ml injection (24.4 +/- 3.6 ml) was smaller than end-diastolic volume at baseline (29.5 +/- 5.8 ml, p < 0.01). Tau after 10-ml injection (39.4 +/- 5.3 msec) was greater than at baseline (35.6 +/- 4.0 msec, p < 0.01). One pig died of ventricular fibrillation after a 20-ml injection of blood. We observed no detrimental effects in Groups III, IV, and V. CONCLUSIONS: More than 10 ml cell suspension compromised diastolic function. We safely performed direct injection of bone marrow cells (1 x 10(8)/1 ml).

Animals↗

Subclinical hypothyroidism and cardiac function.

The cardiovascular system is sensitive to the action of thyroid hormone. However, although a wide spectrum of cardiac abnormalities has long been recognized in patients with overt thyroid dysfunction, the question of cardiac involvement in patients with subclinical thyroid dysfunction has been investigated only in the last two to three decades. Most clinical studies have shown that subclinical hypothyroidism or hyperthyroidism is associated with changes in several cardiac parameters. More specifically, the literature on cardiac involvement in subclinical hypothyroidism consistently shows that patients have resting left ventricular diastolic dysfunction evidenced by delayed relaxation, and impaired systolic dysfunction on effort that results in poor exercise capacity. Whether or not subclinical hypothyroidism also affects left ventricular systolic function at rest remains controversial. Studies of subclinical hypothyroid patients before and after euthyroidism was achieved with levothyroxine replacement provided evidence of impaired resting left ventricular systolic function. Indeed, at-rest left ventricular systolic function was substantially normal in most studies of subclinical hypothyroid patients compared to normal control subjects. Drawing on these data, it appears that subclinical hypothyroidism should be considered a mild form of thyroid failure, associated with initial signs of cardiovascular hypothyroidism. Therefore, it would seem appropriate to initiate timely treatment of patients with mild thyroid failure to prevent cardiac involvement.

Echocardiography, Doppler↗

[Cardiovascular ultrasound: applications for the assessment of cardiac function].

Congestive heart failure(CHF) is usually associated with impaired left ventricular(LV) systolic function, and thus, the measurement of systolic function is an essential component of the evaluation of any patients with known or suspected cardiac disease. Among many parameters, most frequently used are LV percent fractional shortening and ejection fraction(EF), which can be easily measured from an M-mode echocardiogram. However, these M-mode measurements may be inaccurate in patients with asymmetrical LV due to myocardial infarction, right ventricular overload or sigmoid septum. Especially in such cases, EF should be measured using two-dimensional echocardiography. Usually, LV volumes and EF are calculated using the disc-summation method through the manual tracing of apical two-chamber and four-chamber echocardiograms. On the other hand, it has been recognized that congestive heart failure may arise in the absence of any systolic dysfunction and CHF due to systolic dysfunction never occurs in the absence of concomitant diastolic dysfunction. Although the analysis of pulsed-Doppler transmitral flow velocity has been most widely used for the noninvasive assessment of LV diastolic function, an increase in left atrial pressure during CHF can pseudonormalize an abnormal flow pattern and mask LV diastolic dysfunction. Recently, we proposed a new index for assessing LV diastolic function, flow propagation velocity, which can be measured with color M-mode Doppler echocardiography and baseline-shift technique. Recent studies have shown that the flow propagation velocity is a unique noninvasive parameter of LV diastolic function which can accurately detect the diastolic impairment in patients with different types of cardiac diseases with various loading conditions.

Diastole↗