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Relationship between left ventricular morphology and postoperative cardiac function following valve replacement for mitral stenosis.

The left ventricular myocardium excised from 14 patients who had mitral stenosis and who underwent mitral valve replacement was examined, and myocardial fibrosis was quantitated in relation to cardiac function. Conventional mitral valve replacement was performed with cold potassium-induced cardioplegia associated with systemic hypothermia (28 degrees C rectal temperature) and topical cooling. All 14 patients had perivascular fibrosis; the amounts ranged from 16% to 54% of the whole tissue excised. The mean left ventricular end-diastolic volume index (LVEDVI) determined by M-mode echocardiography increased significantly (p less than 0.001) from 66.9 +/- 4.6 ml/m2 preoperatively to 79.0 +/- 2.9 ml/m2 postoperatively. The difference between preoperative and postoperative LVEDVIs was significantly correlated (p less than 0.01) to the percentage of myocardial fibrosis (r = 0.72), in that the index increased postoperatively when myocardial fibrosis was more than 35% and decreased when fibrosis was less than 35%. After mitral valve replacement, the mean ejection fraction increased when fibrosis was less than 35% of whole tissue (+0.12 +/- 0.04) and decreased when fibrosis was greater than 35% (-0.02 +/- 0.02, p less than 0.01). No measured preoperative hemodynamic parameters were predictive of prognosis. These data suggest that the degree of myocardial fibrosis is related to left ventricular performance after mitral valve replacement.

Adult↗

Alterations of phosphorylation state of connexin 43 during hypoxia and reoxygenation are associated with cardiac function.

Gap junctions formed by connexins mediate cell-cell communication by electrical and chemical coupling. Recently, it has been shown that alterations in the phosphorylation state of the connexins result in functional alteration of cell-cell communication through gap junctions. Therefore, we focused on the association of alterations of phosphorylation state of connexin 43 (Cx43) with cardiac function in vivo. Rat hearts were transferred to Langendorff apparatus and submitted to hypoxia and then reoxygenated. In the control heart, Cx43 was phosphorylated and located at the intercalated disk. When the hearts were subjected to hypoxia, Cx43 at gap junctions was dephosphorylated and changed its localization to the entire plasma membrane. The area of cardiomyocytes stained with anti-phosphorylated Cx43 antibody was decreased in a time-dependent manner. Immunoblot data supported the decrease of phosphorylated Cx43 during hypoxia. ZO-1 did not change its localization at the intercalated disk during the hypoxic period. We also found that the area occupied by dephosphorylated Cx43 was correlated with the decrease of percent of rate-pressure product. These data indicate that dephosphorylation and redistribution of Cx43 is an early sign of cardiac injury after hypoxia. Detection of dephosphorylated Cx43 may serve as a diagnostic tool for examining ischemic heart disease.

Animals↗

Serine proteases and cardiac function.

The serine proteases of the trypsin superfamily are versatile enzymes involved in a variety of biological processes. In the cardiovascular system, the importance of these enzymes in blood coagulation, platelet activation, fibrinolysis, and thrombosis has been well established. Recent studies have shown that trypin-like serine proteases are also important in maintaining cardiac function and contribute to heart-related disease processes. In this review, we describe the biological function of corin, tissue kallikrein, chymase and urokinase and discuss their roles in cardiovascular diseases such as hypertension, cardiac hypertrophy, heart failure, and aneurysm.

Animals↗

Influence of basal nitric oxide secretion on cardiac function in man.

1. Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. The purpose of this study was to investigate the effects of basal nitric oxide synthesis on cardiac function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA). 2. Eight normal volunteers were studied on two separate occasions. Measurements of heart rate, blood pressure and echocardiographic indices of left ventricular systolic and diastolic function were made at baseline on each day and every 20 min during incremental infusion of L-NMMA (0.1, 0.2, 0.5, 1.0 and 2.0 mg kg-1 h-1) or placebo. 3. A trend towards reduction in heart rate was observed with L-NMMA infusion although this did not reach statistical significance, whereas significant increases in both systolic blood pressure (at 2.0 mg kg-1 h-1) and systemic vascular resistance index (at 0.5 mg kg-1 h-1) were seen. 4. L-NMMA infusion caused significant reductions in stroke distance and cardiac index, although there was no change in the ratio of end systolic wall stress/end systolic volume index (an afterload independent index of left ventricular systolic performance). 5. The isovolumic relaxation time significantly increased with L-NMMA infusion, together with a significant reduction in the 'E' wave flow velocity integral. Reductions in both peak E/A ratio and E/A flow velocity integral ratio were also seen, although these failed to reach statistical significance. 6. In conclusion, the basal generation of nitric oxide in man appears to maintain a vasodilated state, and modifies left ventricular diastolic filling parameters.

Adult↗

CA 125 and its relation to cardiac function.

BACKGROUND: CA 125, known as a marker for ovarian cancer with hypothetical but hitherto uncharacterized biologic functions, was reported to be elevated in some not-well-defined benign conditions. There are no reports on fluctuations of CA 125 related to cardiac function, especially the failing heart and neurohumoral factors such as norepinephrine or atrial natriuretic peptid/e. METHODS AND RESULTS: CA 125 blood levels were determined in patients with heart failure before and after heart transplantation (HTx). In 71 patients, parallel determinations of norepinephrine, atrial natriuretic peptide, pulmonary capillary wedge pressure, and right atrial filling pressure were done. CA 125 levels also were prospectively studied in patients with heart failure with stabilization (n = 25) or worsening of the clinical status (n = 9) and after HTx (n = 25). Parallel determinations of the tumor markers CEA, CA 199, CA 153, TPS, and TPA were also done. The results were grouped according to the clinical status (New York Heart Association class) of the patients. CA 125 was significantly correlated with neurohormones and filling pressures. Follow-up investigations revealed a decrease of CA 125 levels after HTx (401 +/- 259 U/L vs 33 +/- 22 U/L, P <.001, n = 25) or stabilization (429 +/- 188 U/L vs 78 +/- 35 U/L, P <.001, n = 25) and an increase during worsening of heart failure (42 +/- 25 U/L vs 89 +/- 32 U/L, P <.01, n = 9). In 4 patients after HTx, unexpected death was preceded by rising CA 125 levels. CEA, CA 199, CA 153, TPS, or TPA did not correlate with heart failure status or clinical events. CONCLUSIONS: CA 125 is a marker of the clinical and hemodynamic status and the course of patients with heart failure before and after heart transplantation. The determination of CA 125 serum levels may be an additional tool in the management of these patients. In patients with cancer, these "nonspecific" changes must be considered when CA 125 levels are determined. Whether CA 125 has a specific biologic role in heart failure deserves further studies.

Atrial Natriuretic Factor↗

Does cardiac function modify left heart opacification with transpulmonary echo contrast agents?

Dependence of left heart opacification on ventricular function was evaluated for the new transpulmonary echo enhancing agent (SH U 508-A). The contrast agent was injected intravenously in 5 patients with normal cardiac function (ejection fraction [EF] greater than 60% and echocardiographic left ventricular end-diastolic diameter [LVED] less than 56 mm) and in five patients with pathological ventricular function (EF less than 40%, LVED greater than 65 mm). A concentration of 400 mg/mL with dosages of 5, 9, and 16 mL was used in all patients. The visually assessed signal enhancement as well as the videodensitometrically determined peak intensity and duration of signal enhancement did not differ significantly between the two patient groups, while the transit times were markedly prolonged in patients with impaired ventricular function. No significant alteration was found for systemic blood pressure and heart rate. Side effects were transitory and dose related. The noninvasive nature of the procedure and the absence of hemodynamic effects make repeated studies of left ventricular performance with SH U 508-A in patients with varied hemodynamic status possible.

Aged↗

Influence of acute microwave radiation on cardiac function in normal and myocardial ischemic cats.

Exposure of biological specimens to microwave radiation in vivo and in vitro has been reported to cause alterations to the cardiovascular system. In addition, microwave radiation may cause effects in damaged cardiac tissue that are not observed in normal tissue. In this study, we examined the influence of direct microwave irradiation (2.45 GHz, continuous wave) of the intact exposed heart on cardiac function in cats with and without myocardial ischemia. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery. In the sham-nonexposed and sham-plus-microwave exposed animals the coronary artery was isolated but not occluded. The exposed hearts were either irradiated at a specific absorption rate (SAR) of 30 mW/g or not irradiated, and were monitored for 5 h. At a SAR of 30 mW/g, the temperature of the exposed tissue increased at an initial rate of 0.43 degrees C/min in dead cats. However, in live animals, no increases in aortic blood temperatures occurred during irradiation. Mean arterial blood pressure, cardiac output, heart rate, plasma and myocardial creatine phosphokinase, and S-T segment were not influenced by 5 h of microwave irradiation of the myocardium in cats with or without myocardial ischemia.

Animals↗

Sodium-calcium balance and cardiac function with isotonic iodixanol. An experimental study in the isolated rat heart.

RATIONALE AND OBJECTIVES: Three formulations of the nonionic dimer iodixanol (150/200/300 mg I/mL), made isotonic by the addition of NaCl (70/53/24 mM), were investigated regarding their potential for depressing cardiac contractility during coronary angiography. To maintain a stable cardiac function, the authors sought the requirements for the addition of a balanced amount of calcium (Ca). METHODS: Iodixanol 150, 200, and 300 mg I/mL were applied as a short-lasting bolus in isolated perfused rat hearts in the absence and presence of added Ca. The contractile function was assessed by measurement of changes in left ventricular developed pressure (LVDP). RESULTS: A transient LVDP depression was markedly alleviated by adding 0.2 to 0.4 mM Ca and almost abolished by 0.4 to 0.9 mM. Ca higher than 0.9 mM led to unstable hearts and too-extensive Ca loading. CONCLUSIONS: Caution should be used when adding Ca to iodixanol, particularly with sodium-calcium (Na-Ca) relationships. Appropriate Ca concentrations are probably 0.6 mM for iodixanol (150 mg I/mL); 0.4 to 0.6 mM for iodixanol (200 mg I/mL; and 0.4 mM for iodixanol (300 mg I/mL).

Animals↗

Cardiac function in patients on chronic amiodarone therapy.

Antiarrhythmic agents may depress cardiac contractility and worsen heart failure. Few data are available describing the chronic effects of amiodarone on myocardial function. To assess the effects of amiodarone on cardiac function, we studied 41 consecutive patients with first-pass or equilibrium radionuclide angiography prior to and 3 months after drug therapy was initiated. The mean heart rate, systolic blood pressure (BP), and diastolic BP were not significantly altered by treatment. The mean ejection fraction was 36% +/- 19 (mean +/- 1 SD) at the time of drug initiation and 36% +/- 17 3 months later (p less than 0.05). Nineteen patients had an ejection fraction greater than 30% and 16 had an ejection fraction less than 30%. The mean change in ejection fraction for these two subgroups showed no statistically significant difference, although a decrease in EF greater than 10% was seen in three patients (symptomatic in two), necessitating an increase in diuretic dose. No correlation between amiodarone dose and change in ejection fraction (r = -0.12, p greater than 0.05) was noted. There was no correlation between baseline ejection fraction and change in ejection fraction over this 3-month period (r = -0.36, p greater than 0.05). In summary, amiodarone does not depress left ventricular function and as a result can be used safely in patients with mild to moderate impairment of left ventricular function. In patients with stable left ventricular function, serial tests of left ventricular function may not be necessary.

Adult↗

The effects of chronic ethanol consumption on cardiac function in rats.

A pharmacological model of alcoholism in rats was developed by administering ethanol in their drinking water. This model has provided us with a convenient means to study the effects of chronic ethanol consumption on cardiac functional properties. Our "treated" animals consumed, on the average, an equivalent of 11.1 g/kg of absolute ethanol per day and had an average blood ethanol concentration of 26.9 mg/dL at the end of the 12-week treatment period. The Langendorff-perfused hearts from both treatment and control groups performed equally well mechanically when left to beat spontaneously, but under conditions of electrical pacing the contractile ability of hearts from the alcohol-treated animals deteriorated more rapidly. Dose-response relationships for isoproterenol (isopropylnoradrenaline, IPNA) showed that hearts from alcohol-treated animals did not respond as well as hearts from control animals at higher doses of IPNA. This trend was completely reversed in the presence of low external calcium where the hearts from alcohol-treated animals responded better at all IPNA concentrations. Our observations suggest that chronic alcohol consumption may give rise to alterations in calcium ion handling at the level of myocardial plasma membranes.

Alcoholism↗

Pulmonary and cardiac function in advanced fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva is a rare genetic disease characterized by heterotopic ossification in soft tissues. Severe disability results from progressive immobilization of the limbs, jaw, and chest wall. To determine whether cardiac function is altered in this disease, 25 patients ranging in age from 5 to 55 years (disease duration 1-51 years) were studied. History, physical examination, pulmonary functions, electrocardiography, and echocardiography were performed on each patient. Physical examination of the lungs and heart was unrevealing; no right sided ventricular gallops were heard, and no patient was found to have neck vein distention or peripheral edema. The patients had extremely limited chest expansion (1.9 +/- 0.8 inches), suggesting dependence on diaphragmatic breathing. Lung volumes were severely reduced (mean forced vital capacity 44% +/- 14% of predicted), but flow rates were relatively normal. All patients had normal capillary oxygen saturation. Echocardiography was technically difficult, but no abnormalities of left or right ventricular function were seen. Ten (40%) patients had electrocardiographic evidence of right ventricular dysfunction. Compared with patients without such evidence, these patients were older, had significantly longer disease duration, higher hemoglobin, and more impaired pulmonary function. The results of this study suggest that the presence of severely restrictive chest wall disease is associated with a high incidence of right ventricular abnormalities on electrocardiogram. Whether cor pulmonale will eventually occur remains to be determined.

Adolescent↗

Effects of aminophylline on cardiac function and regional myocardial perfusion: implications regarding its antiischemic action.

Aminophylline improves exercise capacity in patients with angina. Because this drug does not dilate epicardial coronary vessels, its beneficial effect is from either a reduction of myocardial oxygen consumption or an improvement of myocardial blood flow distribution. This study was performed to assess the effects of aminophylline on cardiac function and on regional myocardial perfusion to establish the mechanisms of its antiischemic action. In 10 patients during cardiac catheterization hemodynamic parameters and cardiac volumes were obtained during baseline and after intravenous infusion of aminophylline. Aminophylline decreased left ventricular end-diastolic pressure (from 11 +/- 4 to 4 +/- 2 mmHg, p < 0.001), mean right atrial pressure (from 5 +/- 2 to 2 +/- 1 mmHg, p < 0.01), and left ventricular end-diastolic volume (from 117 +/- 36 to 88 +/- 36 ml, p < 0.01); it increased peak dp/dt (from 1931 +/- 329 to 2430 +/- 540 mmHg/sec, p < 0.001) and heart rate (from 69 +/- 9 to 76 +/- 14 beats/min, p < 0.05) and did not modify systolic aortic pressure (138 +/- 14 vs 137 +/- 16 mmHg, p = not significant [NS]). Estimated oxygen consumption during aminophylline (6.7 +/- 1.3 ml/min/gm) was similar to that during baseline (6.7 +/- 1.4 ml/min/gm). In another study in nine anesthetized dogs with a critical stenosis of the left anterior descending artery, myocardial perfusion was assessed by microspheres during control atrial pacing and during atrial pacing after aminophylline; left atrial pressure was kept constant throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗

Induced hypervolemia, cardiac function, VO2max, and performance of elite cyclists.

OBJECTIVE: To determine whether plasma volume expansion (PVexp) in elite endurance-trained (ET) cyclists, who already possess both a high blood volume (BV) and a high VO2max, leads to further enhancements in their cardiac function, VO2max, and endurance performance (time to exhaustion at 95% VO2max). METHODS: Nine male ET cyclists (V02max = 68.9 +/- 0.6 (SEM) mL x kg(-1) x min(-1)) were studied employing a double blind, cross-over design; i) before PVexp, ii) after sham PVexp (Sham), iii) after restoration of normocythemia, iv) after PVexp (6% dextran), and v) upon reestablishment of normocythemia. RESULTS: PVexp resulted in a 547 +/- 61 mL increase in BV (P < 0.05). Maximal cardiac output and maximal stroke volume were higher (P < 0.05) after PVexp, but the magnitude of these increases was only sufficient to counter the hemodilution effect (lowered O2 content) of PVexp, such that O2 transport, VO2max, and endurance performance remained unchanged. CONCLUSIONS: Expansion of BV in elite ET cyclists, who already possess a high BV, does not improve their VO2max and endurance performance. Elite ET athletes may already be at an optimal BV, which is at or near the limits of their diastolic reserve capacity.

Adult↗

Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder.

OBJECTIVE: Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients. METHODS: Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity. RESULTS: Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine. CONCLUSION: Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.

Adult↗

Endothelin-1 and cardiac function in anthracycline-treated patients: a 1-year follow-up.

Anthracyclines are widely used chemotherapeutic agents in the treatment of lymphomas known to induce cardiomyopathy in more than 20% of patients. There is increasing experimental evidence that cardiac endothelial cells regulate cardiac performance and that endothelin-1 (ET-1) is a central substance in this regulatory mechanism. Twenty (seven male, aged 20-68 years) patients with Hodgkin's or non-Hodgkin's lymphoma treated with anthracycline were followed-up for 1 year. At baseline, after cessation of anthracycline treatment and at 1 year, the plasma ET-1 level was measured by enzyme-linked immunosorbent assay and cardiac function was estimated by echocardiographic measurement of the ejection fraction, the E/A ratio and the deceleration time. The ET-1 level decreased significantly after therapy (5.47 +/- 3.34 pg/mL versus 3.44 +/- 0.69 pg/mL, P < 0.02), and remained significant at 1 year (3.43 +/- 0.57 pg/mL, P < 0.008). The ejection fraction (57.80 +/- 4.73% versus 48.05 +/- 5.65%, P < 0.0001) and the E/A ratio (1.35 +/- 0.40 versus 1.15 +/- 0.40, P < 0.01) decreased, and the deceleration time (177.00 +/- 44.96 ms versus 209.50 +/- 66.25 ms, P < 0.04) increased significantly after therapy, showing that both systolic and diastolic left ventricular performance were deteriorated. Compared with the baseline, the same significant changes were found at 1 year (ejection fraction, 50.65 +/- 8.87%, P < 0.0007; E/A ratio, 1.10 +/- 0.34, P < 0.003; deceleration time, 223.25 +/- 46.85 ms, P < 0.002). The decrease of the ET-1 concentration might be a result of anthracyclines' direct cytotoxic effect and the decreasing level of ET-1 may play a role in the ejection fraction reduction. The results of 1-year follow-up suggest that, although anthracycline toxicity occurs shortly after treatment, the undesirable effect remains.

Adult↗

Cardiac function during induction and early anesthesia with methoxyflurane. An evaluation using systolic time intervals and pressure time indices.

In addition to the standard monitoring of heart rate and blood pressure, the Systolic Time Intervals were used to evaluate cardiac performance, and the Pressure Time Indices (tension time index = TTI; diastolic pressure time index = DPTI) were used to estimate myocardial oxygen balance. Twelve patients with known heart disease were studied during induction with thiopental, intubation, and early anesthesia with methoxyflurane. Cardiac performance diminished after thiopental; and during methoxyflurane it was reflected in increases in pre-ejection period (PEP) and the ratio PEP/LVET. Intubation resulted in a hyperactive state of the heart, as shown by maximal decreases in PEP and PEP/LVET. Myocardial oxygen balance--estimated from the supply/demand ratio (DPTI/TTI)--was impaired after thiopental. After intubation, DPTI/TTI decreased to its lowest value due to an excess of myocardial oxygen demand (TTI) over myocardial oxygen supply (DPTI), signifying a transitory underperfusion of the subendocardium. During methoxyflurane the oxygen balance was gradually restored towards control value. The Systolic Time Intervals and the Pressure Time Indices provided valuable information on cardiac function not available from standard monitoring alone.

Adult↗