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PubMed1980

Monitoring cardiac function with nuclear techniques.

Noninvasive imaging with radioactive tracers has become widely used since its introduction in the early 1970s. Improvements continue to be made in the techniques and the clinical applications. Much of the information provided by these techniques is new. The first transit studies are used mainly in the evaluation of pulmonary transit time, detection of intracardiac shunting, evaluation of right ventricular function, measurement of ejection fraction and detection of wall motion abnormalities at rest and after exercise. The gated blood pool study is found to be most useful in assessment of global left ventricular function, regional wall motion, valve regurgitation and right ventricular function. The techniques of nuclear cardiac imaging are noninvasive, simple, successfully performed in almost 100 percent of cases. They are easy to interpret, able to be quantified and able to be almost totally automated. Their use is likely to become more widespread in the future.

Coronary Disease↗
PubMed2005

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease.

AIMS: The aim of this clinical cross-sectional study was to investigate the cardiac interrelation of morphological and functional abnormalities in patients with Fabry disease. METHODS AND RESULTS: Fifty-one patients (5-78 years) were compared with 25 controls (8-77 years). In all subjects, end-diastolic thickness of the left ventricle was measured by echocardiography and ultrasonic peak systolic strain rate (SR) was extracted to assess regional myocardial function. Magnetic resonance imaging was performed to assess late-enhancement for the detection of myocardial fibrosis in Fabry patients (n=39). In patients, women <20 years of age had no hypertrophy, no late-enhancement, and normal radial and longitudinal function (SR longitudinal=-1.7+/-0.5 s(-1); P=n.s. compared with controls). Ten women, >20 years of age, had no hypertrophy, no late-enhancement, normal radial and longitudinal function in the septal wall, but reduced longitudinal function in the lateral wall (SR=-1.4+/-0.5 s(-1)). All male patients without hypertrophy and no late-enhancement had normal radial function but reduced longitudinal function in both the septal and lateral walls (SR=-1.3+/-0.3 s(-1)). Patients with hypertrophy but without late-enhancement (n=13) had reduced radial and longitudinal function. Twelve patients displaying hypertrophy and late-enhancement had severely reduced radial and longitudinal function (SR=-1.1+/-0.5 s(-1)). Two of them with the worst impairment of regional function (SR=-0.8+/-0.6 s(-1)) died in the follow-up period. CONCLUSION: These results illustrate the variation of morphological changes and its functional consequences in Fabry cardiomyopathy.

Adolescent↗
PubMed1998

[Morpho-functional cardiac evaluation in young normotensive children of hypertensive patients. A prospective Doppler-echocardiographic study].

PURPOSE: Evaluate functional and/or structural cardiac changes in young normotensive subjects with a family history of hypertension. METHODS: Prospective study was performed with 62 normotensive persons, ages 15 to 30 years, divided in 32 children of hypertensive patients (group 1) and 30 children of normotensive persons (group 2) comparable in blood pressure, body surface area, heart rate, age and sex. After clinical examination, all underwent Doppler-echocardiogram to evaluate cardiac structure and left ventricular (LV) systolic and diastolic function. RESULTS: Systolic LV fractional shortening was increased in group 1 when compared with group 2 (38.03 +/- 4.95% and 34.7 +/- 4.48%, respectively--p < 0.01). Mitral deceleration time (DT) ranged from 85 to 160 ms--mean values 116.47 +/- 16.99 ms--in group 1 and from 100 to 220 ms--mean values 126.73 +/- 26.66 ms--in group 2 (p < 0.05). A correlation between LV mass and left atrium (LA) diameter was noted in group 1 (r-0.514, p < 0.01). CONCLUSION: Children of hypertensive patients show increased LV function, similar to what occurs in early hypertension and in borderline hypertension, even when there is no evidence of LV hypertrophy or high blood pressure. Mitral DT (shorten in group 1) was the only diastolic parameter that differed in the groups. The correlation between LV mass and LA dimension suggests that LA size could be related to functional and hemodynamic LV changes.

Adolescent↗
PubMed2000

Overall cardiac functional effect of positive inotropic drugs with differing effects on relaxation.

Recent interest in so-called calcium-sensitizing positive inotropic drugs has highlighted the potential problem of a positive effect on force development being offset, at least partially, by the negative effect that many of these drugs have on relaxation. The purpose of this study was to examine the interplay of contraction and relaxation in determining the overall cardiac effect of different positive inotropic drugs. Using a buffer-perfused isolated rabbit heart preparation, we studied four drugs (calcium, dobutamine, EMD 57033, and CGP 48506) that were given at doses sufficient to increase similarly left ventricular pressure-generating capability by approximately 20%. We show that, even though they produce equivalent changes in pressure-generating capability, these four agents produce dissimilar changes in relaxation capability, with dobutamine speeding relaxation, EMD 57033 slowing relaxation, and calcium and CGP 48506 having little effect of relaxation. Similar relative effects were observed for drug-induced changes in the timing of pressure-generation events. These effects combine to produce different drug-induced changes in overall cardiac pump function judged by the relation between cardiac output and heart rate. Dobutamine shifted the maximal cardiac output to a higher heart rate. In contrast, both calcium sensitizers shifted the maximum in cardiac output to a lower heart rate, whereas calcium had no effect. Thus even though positive inotropic drugs may have similar effects on left ventricular pressure generation, the overall benefit of such drugs on ventricular pump function will depend on how the drug also affects ventricular relaxation and ejection capabilities.

Animals↗
PubMed1982

Pitfalls in the serial assessment of cardiac functional status. How a reduction in "ordinary" activity may reduce the apparent degree of cardiac compromise and give a misleading impression of improvement.

Because the New York Heart Association (NYHA) classification system categorizes patients based on subjective impression of the degree of functional compromise, a reduction in exercise might make a patient seem improved because the new lower level of ordinary activity produced fewer symptoms. To test this hypothesis, we studied three different sets of patients and compared their NYHA classes to their functional classes as determined by a new Specific Activity Scale (SAS) that is based on the metabolic equivalents of oxygen consumption required for activities the patient actually performs. Among ambulatory patients referred for exercise tests, the NYHA class was higher (i.e. indicated the patient was more limited) in 28% of patients and the SAS class was higher in 14% (p less than 0.001). Among patients interviewed at or near the time of catheterization for chest pain, the NYHA was higher in 20% and the SAS class was higher in 20% (p = NS). In both medically and surgically treated patients interviewed 1--3 yr after cardiac catheterization, the NYHA class was higher in only 4%, whereas the SAS class was higher in 28% (p less than 0.001). The SAS class was significantly more likely to be higher in patients who were not working full time and in patients who described their present activity level as sedentary or light. When the NYHA and SAS systems disagreed as to whether a patient was improved, SAS was significantly more likely to correlate with the patient's self-assessment. These findings suggest that some patients restrict their activity as their cardiac disease progresses; the resultant change in the definition of ordinary activity may reduce the apparent degree of cardiac compromise and thus give a false impression of improvement by NYHA criteria.

Activities of Daily Living↗
PubMed2001

Role of fatty acids in the recovery of cardiac function during resuscitation from hemorrhagic shock.

This study tested the hypothesis that removal of fatty acids as a fuel source would improve cardiac efficiency at the expense of reduced cardiac contractile function in the isolated working heart after hemorrhage-retransfusion. Non-heparinized male Sprague-Dawley rats were anesthetized with ketamine-xylazine and were hemorrhaged to a mean arterial blood pressure of 40 mmHg for 1 h. Two-thirds volume of shed blood was reinfused together with 0.9% NaCl in a volume equal to 2.3 times the shed blood volume, followed by continuous infusion of 0.9% NaCl at 10 mL/kg per h for 3 h. Hearts were removed and perfused in closed, recirculating working mode for 60 min to measure hydraulic work and cardiac efficiency. Rates of glycolysis and glucose oxidation were assessed with [5-3H/U-14C] glucose (11 mM) in the absence or presence of 0.4 mM palmitate. Compared to baseline measurements, hemorrhage-retransfusion significantly reduced arterial blood glucose (228+/-7 versus 118+/-12 mg/dL) and non-esterified fatty acid concentrations (0.36+/-0.01 versus 0.30+/-0.02 mM), while elevating blood lactate (0.8+/-0.1 versus 2.5+/-0.4 mM). Perfusion of sham hearts with glucose-only did not alter cardiac work compared to shams perfused with glucose plus palmitate. However, shocked hearts perfused with glucose-only demonstrated a significant reduction in cardiac work compared to shocked hearts perfused with glucose plus palmitate and compared to sham hearts perfused with glucose only (P < 0.05, repeated measures ANOVA). Shocked hearts perfused with glucose plus palmitate showed no reduction in cardiac work compared to shams. Shocked hearts perfused with glucose-only had increased glucose oxidation rates compared to shams perfused with glucose plus palmitate. In sham hearts perfused with glucose-only, myocardial glycogen and triacylglycerol contents were significantly reduced compared to hearts freeze-clamped in situ. These endogenous fuels were not decreased in shocked hearts. These data indicate that hemorrhagic shock renders the heart unable to mobilize endogenous fuels, and suggest that withdrawal of fatty acid oxidation will impair myocardial energy metabolism during resuscitation.

Animals↗
PubMed1992

Cardiac function and myocardial performance of 24-hour-preserved asphyxiated canine hearts.

A method of 24-hour storage of asphyxiated canine hearts for orthotopic cardiac transplantation was studied to expand the geographical size of the donor pool. Left ventricular function of asphyxiated hearts preserved for 24 hours (group 1, n = 8) was compared with that of hearts donated on-site (group 2, n = 5). Group 1 donors were pretreated with verapamil hydrochloride, propranolol hydrochloride, and prostacyclin. The donor hearts were perfused with warm blood cardioplegia in situ after 10 minutes of asphyxiation and then perfused with cold crystalloid cardioplegia for 2 hours. The hearts were excised and stored in ice-cold University of Wisconsin solution for 22 hours. At orthotopic transplantation, coronary perfusion with warm blood cardioplegia was performed before the graft aorta was unclamped. Conventional cardiac variables (eg, cardiac output and maximum rate of rise of left ventricular pressure), myocardial performance, and diastolic compliance of grafted hearts were assessed 1 hour after weaning from bypass. All recipients in both groups were easily weaned from cardiopulmonary bypass without inotropic agents, and there were no significant differences in cardiac variables between the two groups. These results strongly suggest that cadaver hearts can be preserved for 24 hours with satisfactory cardiac function.

Animals↗
PubMed1975

Is early decline of cardiac function in ischaemia due to carbon-dioxide retention?

There is no satisfactory explanation for the early and rapid decline of cardiac muscle function in ischaemia. Reduction of the energy source for contraction, A.T.P., is insufficient in magnitude and too slow in onset to be the prime cause. It is proposed that a large part of the loss of function is directly attributable to an immediate fall of intracellular pH and results from the accumulation of carbon dioxide and lactic acid; the intracellular acidosis reduces myocardial function by inhibition of that part of the calcium-ion influx associated with contraction.

Acidosis↗
PubMed1999

Autologous heart cell transplantation improves cardiac function after myocardial injury.

BACKGROUND: Fetal ventricular cardiomyocyte transplantation into a cardiac scar improved ventricular function, but these cells were eventually eliminated by rejection. We therefore examined the feasibility of autologous adult heart cell transplantation. METHODS: A transmural scar was produced in the left ventricular free wall of adult rats by cryoinjury. The left atrial appendage was harvested, and the atrial heart cells were cultured and their number expanded ex vivo. Three weeks after cryoinjury, either a cell suspension (2 x 10(6) cells, n = 12 rats, transplant group) or culture medium (n = 10 rats, control group) was injected into the scar. Rats having a sham operation (n = 5) did not undergo cryoinjury or transplantation with cells or culture medium. RESULTS: Five weeks after injection, ventricular function was evaluated in a Langendorff preparation, measuring systolic, diastolic, and developed pressures over a range of intraventricular balloon volumes. Systolic and developed pressures were greater in the transplant group than in the control group (p = 0.0001). Rats with a sham operation had the greatest systolic, diastolic, and developed pressures (p = 0.0001). Histologic studies demonstrated survival of the transplanted heart cells within the scar. The area of the scar was smaller (p = 0.0003) and its thickness greater (p = 0.0003) in rats in the transplant group. Left ventricular chamber volume was smaller in the transplant group (p = 0.043). CONCLUSIONS: Transplantation of autologous cultured adult atrial heart cells limited scar thinning and dilatation and improved myocardial function compared with results in control hearts. This technique may lead to a novel therapy to prevent scar expansion after a myocardial infarction and prevent the development of congestive heart failure.

Animals↗
PubMed2006

Synergistic activation of salmon cardiac function by endothelin and beta-adrenergic stimulation.

The aim was to find out the effects of endothelin-1 (ET-1) in salmon (Salmo salar) cardiac contractile and endocrine function and its possible interaction with beta-adrenergic regulation. We found that ET-1 has a positive inotropic effect in salmon heart. ET-1 (30 nM) increased the contraction amplitude 17+/-4.7% compared with the basal level. beta-Adrenergic activation (isoprenaline, 100 nM) increased contraction amplitude 30+/-13.1%, but it did not affect the contractile response to ET-1. ET-1 (10 nM) stimulated the secretion of salmon cardiac natriuretic peptide (sCP) from isolated salmon ventricle (3.3+/-0.14-fold compared with control) but did not have any effect on ventricular sCP mRNA. Isoprenaline alone (0.1-1,000 nM) did not stimulate sCP release, but ET-1 (10 nM) together with isoprenaline (0.1 nM) caused a significantly greater increase of sCP release than ET-1 alone (5.4+/-0.07 vs. 3.3+/-0.14 times increase compared with control). The effects on the contractile and secretory function could be inhibited by a selective ETA-receptor antagonist BQ-610 (1 microM), whereas ETB-receptor blockage (by 100 nM BQ-788) enhanced the secretory response. Thus ET-1 is a phylogenetically conserved regulator of cardiac function, which has synergistic action with beta-adrenergic stimulation. The modulatory effects of ET-1 may therefore be especially important in situations with high beta-adrenergic tone.

Adrenergic beta-Agonists↗
PubMed2004

Effects of interferon-alpha therapy on cardiac function in patients with chronic hepatitis B infection.

Various types of cardiovascular complications, such as myocardial infarction, cardiac arrhythmias, cardiomyopathy, and myocarditis attributed to interferon therapy have been reported. The aim of this study was to evaluate the cardiac effects of interferon-alpha (IFN-alpha) in patients with chronic hepatitis B infection. Forty-five patients with chronic hepatitis B infection (41 men and 3 women; mean age 34.2 +/- 11.5 years) were included in the study, and 10MU IFN-alpha 2b was administered three times a week for 6 months to the patients. Cardiac evaluation (detailed medical history, physical examination, electrocardiography, systolic and diastolic function parameters by echocardiography) was performed at the beginning, and at the 1st, 3rd, and 6th months of therapy. No patients had any cardiac symptoms during interferon therapy, and systolic and diastolic blood pressure and heart rate were not significantly affected (P > 0.05). None of the patients revealed cardiac rhythm disturbance on electrocardiography before or during the therapy period. No significant changes were detected in systolic (ejection fraction, fractional shortening, pre-ejection period, left ventricular ejection time, the ratio of pre-ejection period/ejection time, Q-V peak) and diastolic (E peak, A peak of transmitral flow velocity, E/A ratio, deceleration time, isovolumic relaxation time by conventional echocardiography, and E peak, A peak, deceleration time of E wave at the medial and lateral corners of the mitral annulus by tissue Doppler echocardiography) left ventricular function parameters between the beginning and the 1st, 3rd, and 6th months of therapy. The results of this study suggest that IFN-alpha therapy does not cause a significant deterioration in cardiac function in patients with chronic hepatitis B infection, and it may be used safely in patients without cardiac disease.

Adult↗
PubMed2006

Restoration of cardiac function with progenitor cells.

The biological limitations to cardiac regenerative growth create a clinical need to promote more efficient cardiac repair. Experimental studies and early-phase clinical trials indicate that progenitor cells may be useful as a therapeutic tool to improve heart function after myocardial ischaemia. This paper will summarize experimental studies to determine (1) the mechanisms underlying progenitor cell homing to ischaemic tissue and (2) to define transcription factors involved in endothelial maturation of progenitor cells. Homing seems to be assisted by a proteolytic enzyme, cathepsin L, which degrades the extracellular matrix. In an in vitro assay, a cathepsin inhibitor prevented different progenitor cell populations from passing through a matrigel layer. In vivo, progenitor cells lacking cathepsin L had an impaired capacity to promote neovascularization in ischaemic mouse limbs compared with normal, wild-type cells. Differentiation of progenitor cells towards the endothelial phenotype involves a member of the homeobox gene family, HoxA9. HoxA9 regulates endothelial gene expression (eNOS, KDR, VE-cadherin). Moreover, HoxA9-deficient mice have a severe impairment of neovascularization capacity after ischaemia. In the second part of the paper, we describe clinical studies using bone marrow or the peripheral blood-derived cells for functional recovery of patients with acute and chronic heart failure (TOPCARE-AMI, TOPCARE-CHF). Whereas blood-derived and bone marrow-derived progenitor cells were equally effective in patients with acute myocardial infarction, bone marrow-derived cells were significantly better than blood-derived progenitor cells in patients with chronic ischaemic heart disease.

Animals↗
PubMed1998

Reliability of noninvasive methods to measure cardiac autonomic function.

Cardiac autonomic modulation was examined in 10 healthy subjects (mean age = 27.8 +/- 1.7) at rest (paced breathing at 12 and 16 breaths/min) and during a submaximal cycle ergometer exercise test. Heart rate variability (HRV) spectral parameters and spontaneous baroreflex (SBR) function variables showed no significant differences between mean values for any of the testing conditions. Spectral parameters and SBR function did not differ significantly between the resting conditions. Significant reliability coefficients (r = 0.59-0.73) were observed for all spectral parameters except low frequency power (r = 0.22) during 12 breaths/min, with moderately lower values during 16 breaths/min (r = 0.10-0.75) and exercise (r = 0.20-0.89). Significant reliability coefficients were observed for baroreflex sensitivity at 12 (r = 0.83) and 16 (r = 0.92) breaths/min. It was concluded that at rest, HRV spectral and SBR analyses are reliable methods for studying cardiac autonomic balance.

Adult↗
PubMed1982

Irreversible morphological changes contributing to depressed cardiac function after surgery for chronic aortic regurgitation.

The timing of surgery in chronic aortic regurgitation remains a difficult problem. To identify variables predictive of postoperative haemodynamic improvement, changes in left ventricular mass, volume, morphology, and histochemistry were analysed in 67 patients undergoing surgery for chronic aortic regurgitation. Patients were divided into two groups: those in whom the left ventricular echo diameters returned to normal after operation (51 patients, group A), and those with postoperative dilatation (16 patients, group B). A preoperative biopsy was obtained in all patients; postoperative tissue samples were available in 13 patients (five from group A, eight from group B). Data were correlated with the postoperative clinical, haemodynamic state over a follow-up period of three years. Regression of hypertrophy was usually incomplete. Echocardiographic and angiographic data could not define the type and degree of dysfunction which was irreversible. Massive fibre hypertrophy (mean 34.1 micrometers), moderately or severely increased interstitial fibrous tissue, reduced levels of the myofibrillar and mitochondrial enzymes adenosine triphosphates and succinate dehydrogenase in pre- and post-operative tissue samples correlated with persistent dilation, cardiac failure, and early death (group B). Irreversible morphological and functional changes contributed to a depressed cardiac function after operation. Preoperative ventricular biopsies are thus of prognostic importance in volume overload.

Adolescent↗
PubMed1982

Cardiac function in end-stage renal disease.

To assess cardiac status in end-stage renal disease, we compared clinical, ECG, and echocardiographic data from 37 patients on maintenance hemodialysis with data from 42 patients with functioning renal transplants. Cardiovascular symptoms and abnormal cardiovascular findings were more common in dialysis-maintained patients than in those with transplants. Follow-up studies indicated that despite a high prevalence of cardiac symptoms, abnormal physical signs, and dilated left ventricles among patients with end-stage renal disease, systolic left ventricular function was generally well preserved irrespective of renal failure therapy. Compared with maintenance hemodialysis, however, successful renal transplantation is associated with an overall enhancement of cardiac status, the majority of which is probably secondary to transplant-associated improvement in hemoglobin level and control of intravascular volume.

Adolescent↗
PubMed2000

Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene.

Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.

Acromegaly↗