Biomedical subjects

H Just

Publications and source records attributed to H Just.

At least 73 records · Page 4Linked to original sources

PubMed1996

Calcium cycling proteins and force-frequency relationship in heart failure.

Myocardial function, intracellular calcium and levels of calcium cycling proteins were analyzed in failing and nonfailing human myocardium. Myocardial function was evaluated by the isometric force-frequency relation, and intracellular calcium was studied by aequorin light emission. When stimulation frequency was increased above 30 min-1, there was a continuous increase in isometric tension development in the nonfailing myocardium. In contrast, in failing myocardium, frequency potentiation of contractile force was blunted or inverse. As a consequence, at higher rates of stimulation, twitch tension was reduced significantly in failing compared to nonfailing human myocardium. Aequorin measurements indicated that the contractile deficit in the failing myocardium at higher rates of stimulation is associated with decreased free intracellular calcium concentration. Western blot analysis indicated that in the failing myocardium protein levels of SR-Ca(2+)- ATPase are significantly reduced and protein levels of Na(+)-Ca(2+)- exchanger are significantly increased. Levels of phospholamban are slightly reduced in the failing myocardium, and ryanodine receptor and calsequestrin protein levels are unchanged. There was a close positive correlation between the protein levels of SR-Ca(2+)-ATPase and frequency potentiation of contractile force. From these data, we conclude that in failing compared to nonfailing human myocardium 1) force-frequency relation is blunted or inverse. 2) Frequency-dependence of contractile force is closely correlated with frequency-dependence of intracellular calcium cycling. 3) Protein levels of SR-Ca(2+)-ATPase may determine frequency-dependence of sarcoplasmic reticulum calcium release. 4) Calcium elimination by an increased number of Na(+)-Ca2-exchanger molecules may be a compensatory mechanism to prevent diastolic calcium accumulation in failing myocardium with a reduced number of SR calcium pumps.

Calcium↗

PubMed1996

Scoring system for nosocomial pneumonia in ICUs.

OBJECTIVE: To develop a scoring system for stratifying patients in intensive care units (ICUs) by risk of developing nosocomial pneumonia (NP), based on variables generally available in an ICU, and to determine the probability of a patient developing NO in the ICU. DESIGN AND SETTING: a 2-year prospective cohort study conducted in a medical and surgical ICU. PATIENTS: 756 patients admitted to the ICU for 48 h or more were followed up until the development of NP or death or discharge from the ICU. MEASUREMENTS AND RESULTS: 129 (17.1%) patients developed NP, 106 (14%) in the first 2 weeks. The following independent risk factors were identified by multivariate analysis: no infection on admission [relative risk (RR) = 3.1, 95% confidence intervals (CI) = 2.0 to 4.81; thorax drainage (RR = 2.1, 95% CI = 1.2 to 3.5); administration of antacids (RR = 2.1, 95% CI = 1.4 to 3.1); partial pressure of oxygen (PO2) > 110 mmHg (RR = 1.6, 95% CI = 1.0 to 2.6); administration of coagulation factors (RR = 1.8 95% CI = 1.0 to 3.2); male gender (RR = 2.7, 95% CI = 1.2 to 6.3); urgent surgery (RR = 2.4, 95% CI = 0.9 to 6.4); and neurological diseases (RR = 4.2, 95% CI = 1.9 to 9.4). To obtain a predictive risk index for NP, a scoring system was developed using a multivariate model. The probability of developing NP varied between 11.0% in the lowest risk group and 42.3% in the highest risk group. The patients' risk of acquiring NP was seven times higher in the highest score category (i.v.) than in the lowest one (I). CONCLUSIONS: ICU patients can be stratified into high- and low-risk groups for NP. No infection on admission, thorax drainage, administration of antacids, and PO2 > 110 mmHg were associated with a higher risk of NP during the entire 2-week period.

Adult↗

PubMed1996

Dissociation of coronary vascular tolerance and neurohormonal adjustments during long-term nitroglycerin therapy in patients with stable coronary artery disease.

OBJECTIVES: We sought to examine whether long-term nitroglycerin treatment causes tolerance in large coronary arteries and whether the loss of vascular effects parallels neurohormonal adjustments. BACKGROUND: Nitroglycerin therapy is associated with increased plasma renin activity and aldosterone levels and a decrease in hematocrit. It is assumed that nitroglycerin tolerance results in part from these neurohormonal adjustments and intravascular volume expansion. METHODS: Three groups were studied: group I (n = 10), no prior nitroglycerin therapy; and group II (n = 10) and group III (n = 8), 24- and 72-h long-term nitroglycerin infusion (0.5 micrograms/kg body weight per min), respectively. Coronary artery dimensions were assessed using quantitative angiography. Plasma renin activity, plasma aldosterone and vasopressin levels and hematocrit were monitored before and during nitroglycerin infusions. RESULTS: In group I, increasing intravenous concentrations of nitroglycerin caused a dose-dependent increase of the midportion of the left anterior descending coronary artery (baseline diameter 2.13 +/- 0.07 mm [mean +/- SEM], maximally by 22 +/- 2%) and left circumflex coronary artery (baseline diameter 2.08 +/- 0.07) mm, maximally by 22 +/- 3%). An intracoronary nitroglycerin bolus (0.2 mg) caused no further significant increase in diameter, indicating maximal dilation. In group II (n = 10), the baseline large coronary artery diameter under ongoing nitroglycerin was significantly larger than that in group I (left anterior descending artery 2.61 +/- 0.08 mm, left circumflex artery 2.57 +/- 0.08 mm). Additional intravenous and intracoronary nitroglycerin challenges did not cause further dilation, indicating maximally dilated vessels. At the same time, plasma renin activity, plasma aldosterone and vasopressin levels were significantly increased, and hematocrit significantly decreased. In group III patients, the baseline diameter of the left anterior descending artery and the left circumflex artery did not differ from that in patients without nitroglycerin pretreatment, indicating a complete loss of nitroglycerin coronary vasodilative effects. These patients showed no significant increase in circulating neurohormonal levels but a significant decrease in hematocrit. CONCLUSIONS: Within 24 h of continuous nitroglycerin treatment, the coronary arteries were maximally dilated despite neurohormonal adjustments and signs of intravascular volume expansion. Within 3 days of nitroglycerin infusion, tolerance developed in the absence of neurohormonal activation. The dissociation of neurohormonal adjustments and tolerance in large coronary arteries indicates that after long-term nitroglycerin treatment, true vascular tolerance, perhaps from an intracellular tolerance step, may have developed.

Aldosterone↗

PubMed1996

Modulation of myocardial economy and efficiency in mammalian failing and non-failing myocardium by calcium channel activation and beta-adrenergic stimulation.

OBJECTIVE: We investigated the energy-metabolic consequences of positive inotropic stimulation by the calcium channel activator, BAY K 8644, in comparison with isoprenaline, focussing both on the economy of force development and the efficiency of external work. METHODS: In the first instance, heat liberation was measured in isometrically contracting right ventricular papillary muscles from guinea pigs by means of antimony-bismuth thermopiles; in the second instance, external work and myocardial oxygen consumption were analyzed in isolated failing and non-failing working rat hearts. RESULTS: In the guinea pig muscle strip preparations BAY K 8644 (10(-5) M) and isoprenaline (10(-8 M) increased peak developed force from 13.7 +/- 2.7 to 37.6 +/- 14.9 mN/mm2 and from 13.6 +/- 5.2 to 38.8 +/- 3.3 mN/mm2, respectively (P < 0.01). Stress-time integral was increased from 10.3 +/- 3.0 to 34.7 +/- 19.2 mN.s/mm2 by BAY K 8644 and from 9.5 +/- 2.4 to 23.0 +/- 1.6 mN.s/mm2 by isoprenaline. Whereas a significant decrease in the ratio between stress-time integral and initial heat (integral of Pdt/IH) (i.e., economy contraction) was observed for isoprenaline (5.26 +/- 1.91 before and 3.11 +/- 0.72 N.m.s.J-1 after treatment (P < 0.01), BAY K 8644 did not significantly alter this index (5.26 +/- 2.39 before and 6.22 +/- 2.63 N.m.s.J-1 after treatment). Similar results were obtained for the ratio between stress-time integral and tension-dependent heat. Significantly more calcium ions were required for equieffective activation of the contractile proteins with isoprenaline as compared to BAY K 8644. In working preparations of sham-operated and infarcted rat hearts, the increase in myocardial oxygen consumption per minute (delta MVO2) for a given increase in external work per minute (delta P) was significantly higher with isoprenaline than with equipotent concentrations of BAY K 8644 or high calcium. CONCLUSIONS: Inotropic mycardial stimulation by BAY K 8644 is associated with higher economy and efficiency than stimulation by isoprenaline when analyzed both by heat measurements in isometric preparations and by myocardial oxygen consumption in working heart preparations.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1996

Pathophysiological targets for beta-blocker therapy in congestive heart failure.

The treatment of congestive heart failure has seen considerable changes: while treatment with diuretics, digitalis glycosides and vasodilators has remained the mainstay of therapy, recently neurohumeral inhibition has been developed as an important principle: ACE-inhibitors have been shown to significantly improve quality of life and exercise performance and to substantially reduce mortality. Beta-blockers have been employed with increasing success mainly in congestive heart failure due to dilated idiopathic cardiomyopathy, in which a significant improvement in symptoms and life expectancy has been demonstrated. However, the precise mechanisms by which beta-blockade improves congestive heart failure remain to be elucidated. In addition to direct sympathoadrenal inhibition, reduction of heart rate may also play a major role in the therapeutic efficacy of beta-blockade in congestive heart failure. In the normal human heart increase in heart rate is accompanied by an increase in myocardial contractile performance (Bowditch-Treppe phenomenon). In chronic heart failure the myocardium undergoes a phenotype change which includes alterations of the activity of enzymes regulating calcium homoeostasis. The sarcoplasmic reticulum calcium ATPase (SERCA) is depressed both in function, as well as in expression. At the same time the sarcolemmal sodium-calcium exchanger is increased both in function and in expression. The result is a characteristic change in calcium homoeostasis with decreased diastolic uptake of calcium into the sarcoplasmic reticulum with subsequently reduced calcium release during the next systole, resulting in reduced contractile performance. At the same time increased capacity of the sodium-calcium exchanger extrudes intracellular calcium ions to the extra-cellular space, thereby rendering these ions unavailable for the contractile cycle. A result of these, seemingly specific, phenotype changes is an alteration of the force/frequency relationship. Instead of increasing force of contraction with increasing heart rates, in the chronically failing myocardium the contractile performance declines with increasing heart rates and only improves with decreasing rates. Optimal performance can be seen at heart rates as low as 30 beats.min. Studies employing photoluminescence markers of free cytosolic calcium, such as aequorin, have shown that there is a direct correlation between free cytosolic calcium and contractile performance at different levels of heart rate. It is likely, therefore, that the heart rate reduction with beta-blockade may provide the major explanation for the therapeutic benefits of beta-blockade in chronic congestive heart failure.

Adrenergic beta-Antagonists↗

PubMed1996

Calcium antagonist drugs in hypertensive patients with angina pectoris.

Arterial hypertension frequently occurs in association with myocardial ischaemia and is an independent and significant risk factor for the development of coronary artery disease (CAD), as is left ventricular hypertrophy due to arterial hypertension. The prevalence of CAD in patients with hypertension is high, while hypertension occurs in approximately 60% of patients with CAD. Myocardial ischaemia occurs both in the presence and absence of CAD, probably as the result of limitation of coronary vasodilator capacity and reduction in coronary flow. This may occur in hypertension due to increased transmural coronary artery resistance, alterations in the vascular wall and endothelial dysfunction. Furthermore, left ventricular hypertrophy itself predisposes the heart towards ischaemia due to an increased diffusion distance between capillaries. When myocardial ischaemia occurs in hypertensive patients, 90% of all episodes are aysmptomatic. The highest incidence of ischaemic episodes appears to occur in treated elderly hypertensive men with inadequate blood pressure control (40%). Calcium antagonists exert a range of beneficial effects in hypertensive patients, including reduction of blood pressure, improvement in myocardial blood flow, regression of left ventricular hypertrophy and cardioprotection in reperfused organs. However, while vasoprotective effects have been demonstrated in animal models, beneficial effects in man are uncertain. Thus, in established coronary atherosclerosis, calcium antagonist treatment has produced only a mild reduction in the appearance of new atherosclerotic lesions.

Angina Pectoris↗

PubMed1996

Adenosine in treating cardiac arrhythmias.

1. Adenosine is an endogenous nucleoside which causes a brief blockade of the AV nodal conduction pathway following intravenous administration. 2. Such a brief AV block can be used therapeutically for reliable termination of AV nodal re-entry tachycardia and WPW re-entry tachycardia. It can also be used for demasking atrial activity in rapid suspected supraventricular tachycardia with a broad QRS complex or a Delta wave, not present during sinus rhythm with normal AV node conduction, indicating the presence of a hidden WPW syndrome. 3. Side effects after adenosine application are frequent, but very transient rarely serious (1-3% of cases, e.g. status asthmaticus, ventricular fibrillation) and therefore require a certain degree of experience with this drug on the part of the treating physician.

Adenosine↗

PubMed1996

Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial.

PRIMARY OBJECTIVE: To determine the effects of pimobendan 2.5 and 5 mg daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, placebo controlled trial of the addition of pimobendan to conventional treatment with a minimum follow up of 24 weeks. SETTING: Outpatient cardiology clinics in six European countries. PATIENTS: 317 patients with stable symptomatic heart failure, objectively impaired exercise capacity, and an ejection fraction of 45% or lower who were treated with at least an angiotensin converting enzyme inhibitor and a diuretic and who tolerated a test dose of pimobendan. RESULTS: Compared with placebo, both pimobendan 2.5 and 5 mg daily improved exercise duration (bicycle ergometry) by 6% (P = 0.03 and 0.05) after 24 weeks of treatment. At that time 63% of patients allocated to pimobendan and 59% of those allocated to placebo were alive and able to exercise to at least the same level as at entry (P = 0.5). No significant effects on oxygen consumption (assessed in a subgroup of patients) and on quality of life (assessed by questionnaire) were observed. Pimobendan was well tolerated. Proarrhythmic effects (24-hour electrocardiography) were not observed. In both pimobendan groups combined the hazard of death was 1.8 (95% confidence interval 0.9 to 3.5) times higher than in the placebo group. CONCLUSIONS: Pimobendan improves exercise capacity in patients with chronic heart failure who are also on conventional treatment. The balance between benefit and risk of treatment with this compound remains to be established however.

Aged↗

PubMed1996

Diagnosis, localization and evaluation of malignancy of heart and mediastinal tumors by conventional and transesophageal echocardiography.

Transesophageal echocardiography is well established in detecting and diagnosing heart tumors. In contrast, its role in assessing presence, growth and evidence of malignancy of tumors originating from the mediastinal site remains widely uncertain. In a prospective and investigator-blind study, we evaluated 72 consecutive patients with cardiac and/or mediastinal tumor lesions to assess the diagnostic impact of transthoracic and transesophageal echocardiography in determining localization, growth and malignancy. All tumor lesions were diagnosed and carefully evaluated by computer tomography and/or magnetic resonance imaging prior to the study. Biopsy demonstrated a malignant tumor in 49 patients and a benign tumor in 23 patients. Transthoracic and transesophageal echocardiography were equally effective in visualizing tumors of the heart in 24 patients (92% vs 100%; N.S.). Tumors originating from the mediastinum were 2.9 times less likely to be detected by the transthoracic approach (p < 0.001). In these patients, transesophageal echocardiography was also superior in diagnosing myocardial infiltration (18 vs 4 patients, p < 0.001) and invasion or intracardiac growth of the tumor (13 vs 6 patients, p < 0.05). When compared to histological findings, transesophageal echocardiography predicted malignancy from the presence of tumor spread both in- and outside the heart, infiltration and invasion in 21/49 patients (43%), a false positive result was obtained in only 1/23 patients with a benign tumor. Conventional echocardiography predicted malignancy in only 4/49 patients (8%, p < 0.005). In conclusion, transesophageal echocardiography is increasingly used in patients with suspected mediastinal tumor lesions. Our study demonstrates, that transesophageal echocardiography is effective and superior to the conventional approach in predicting localization and growth of mediastinal tumors, as well as in accessing evidence of malignancy of the tumor.

Echocardiography↗

PubMed1996

[Diagnostic value of various echo- and Doppler echocardiography methods in quantifying mitral valve stenosis].

UNLABELLED: Two-dimensional and Doppler echocardiography have been widely used for noninvasive determination of valve area in patients with mitral stenosis. Recent studies have indicated that the Doppler-echocardiographic pressure half-time method (PHT) does not accurately predict mitral orifice area (MOA). Therefore, applications of the continuity equation and the Gorlin formula have been used additionally to the PHT for Doppler-echocardiographic assessment of MOA. In a prospective study of 34 patients MOA determined by two-dimensional and Doppler echocardiography was compared with MOA measured by cardiac catheterization (range 0.40 to 1.90 cm2, mean 1.08 +/- 0.37 cm2). There was a moderate correlation between two-dimensional echocardiographic and invasive measurements (r = 0.65, SEE = 0.20 cm2). MOA calculated by the PHT showed only poor correlation with cardiac catheterization (r = 0.38 SEE = 0.37 cm2). We found better correlations for the continuity equation (r = 0.73, SEE = 0.35 cm2) and Doppler-echocardiographic application of the Gorlin formula (r = 0.81, SEe = 0.27 cm2). Doppler-echocardiographic use of the Gorlin formula yielded the best prediction of the severity of mitral valve stenosis (concordance with invasive measurement in 82%). CONCLUSION: Pressure half-time is only a poor predictor of the severity of mitral valve stenosis. More accurate results are obtained by Doppler-echocardiographic applications of the continuity equation and especially the Gorlin formula.

Adult↗

PubMed1996

[Value of beta-blocker therapy in treatment of coronary heart disease and sudden cardiac death with special reference to carvedilol].

Beta-blocking agents are well established in the treatment of patients with coronary artery disease. Synergistic effects on mortality, myocardial ischemia, the risk for myocardial (re-)infarction and, as most recently shown, on sudden cardiac death form the basis for the convincing prognostic impact of these agents. The present paper is directed to summarize the clinical evidence for the therapeutic benefit of beta-blocking agents in post-infarction patients, to characterize subgroups of patients who will benefit most from such a therapeutic intervention and to discuss the present impact of newer beta-blocking agents, such as carvedilol which beside its effects on beta-1 and beta-2 receptors exerts potent vasodilating properties via an alpha-1 receptor blockade.

Adrenergic beta-Antagonists↗

PubMed1995

Role of endogenous bradykinin in human coronary vasomotor control.

BACKGROUND: Bradykinin is a potent vasodilator that acts through B2 kinin receptors to stimulate the release of endothelium-derived nitric oxide, prostacyclin, and hyperpolarizing factor. In this study, we investigated the contribution of endogenous bradykinin to vasomotor control in the human coronary circulation. METHODS AND RESULTS: The selective bradykinin B2 receptor antagonist HOE 140 was infused into the left main coronary artery (200 micrograms/min for 15 minutes) in 15 patients without significant coronary stenoses. Epicardial responses were evaluated by quantitative coronary blood flow with a Doppler flow-velocity wire. Flow-dependent dilation (n = 10; intracoronary papaverine) and acetylcholine responses (n = 5) were assessed before and after HOE 140. After HOE 140, there was a reduction in luminal area in the proximal (P < .001), mid (P < .001), and distal (P < .05) coronary arteries. HOE 140 led to an increase in coronary vascular resistance (P < .001) and a decrease in coronary blood flow (P < .001). After bradykinin B2 receptor blockade, there was a reduction in flow-dependent dilation (23.4 +/- 6.9% to 3.9 +/- 6.0%, P < .001), the extent of which correlated with the degree of basal vasoconstriction after HOE 140 in the same vessel segment (P < .05). Acetylcholine responses were unchanged after HOE 140. CONCLUSIONS: The results of this study demonstrate for the first time a role for endogenous bradykinin in mediating normal vasomotor responses in resistance and epicardial coronary vessels under basal and flow-stimulated conditions in the human coronary circulation.

Animals↗

PubMed1995

Effect of long-term angiotensin-converting enzyme inhibition on vascular function in patients with chronic congestive heart failure.

The present study demonstrates that peripheral vasodilatory capacity is impaired in patients with chronic congestive heart failure not treated with aspirin, but preserved in patients taking aspirin. This decreased peripheral vasodilatory capacity can be restored by chronic angiotensin-converting enzyme inhibition, indicating that locally acting cyclooxygenase-dependent factors contribute to peripheral vasoconstriction in chronic congestive heart failure.

Adult↗

PubMed1995

Positive and negative inotropic effects of DL-sotalol and D-sotalol in failing and nonfailing human myocardium under physiological experimental conditions.

BACKGROUND: DL-Sotalol has class III antiarrhythmic activity through prolongation of the repolarization phase of the action potential as well as beta-adrenoceptor-blocking properties. Although the former effect was found to exert positive inotropic effects in animal experimental studies, the latter may be detrimental in heart failure due to negative inotropism. In contrast to DL-sotalol, D-sotalol is suggested to exert only positive inotropic effects, which were never tested in isolated human myocardium. METHODS AND RESULTS: Therefore, we investigated the effects of racemic DL-sotalol and its enantiomer D-sotalol in human right atrial muscle strip preparations and in left ventricular muscle strip preparations from nonfailing and end-stage failing human hearts. DL-sotalol and D-sotalol significantly (P < .01) increased peak developed force in atrial preparations by 14.0 +/- 3.4% and 16.7 +/- 3.8%, respectively, but had no effect in ventricular myocardium. In nonfailing ventricular myocardium, both DL-sotalol and D-sotalol shifted the dose-response curve for isoproterenol to higher concentrations (P < .01); however, DL-sotalol was 100-fold more effective than D-sotalol. In non-failing myocardium, a positive force-frequency relation was found between 30 and 120 beats per minute, but isoproterenol was much more powerful in its inotropic effects. In failing myocardium, reduction in stimulation rate from 120 to 30 beats per minute increased peak developed force more pronounced than did the application of isoproterenol. CONCLUSIONS: (1) D-Sotalol has no relevant beta-adrenoceptor-blocking activity compared with DL-sotalol. (2) Neither DL-sotalol nor D-sotalol exhibit positive inotropic effects in human left ventricular myocardium. (3) Heart rate reduction increases contractile force in end-stage failing human myocardium due to an inverse force-frequency relation and thereby counteracts the potential negative inotropic properties of beta-blockade.

Adrenergic beta-Agonists↗

PubMed1995

Alterations in intracellular calcium handling associated with the inverse force-frequency relation in human dilated cardiomyopathy.

BACKGROUND: The present study was performed to test the hypothesis that the altered force-frequency relation in human failing dilated cardiomyopathy may be attributed to alterations in intracellular calcium handling. METHODS AND RESULTS: The force-frequency relation was investigated in isometrically contracting ventricular muscle strip preparations from 5 nonfailing human hearts and 7 hearts with end-stage failing dilated cardiomyopathy. Intracellular calcium cycling was measured simultaneously by use of the bioluminescent photoprotein aequorin. Stimulation frequency was increased stepwise from 15 to 180 beats per minute (37 degrees C). In nonfailing myocardium, twitch tension and aequorin light emission rose with increasing rates of stimulation. Maximum average twitch tension was reached at 150 min-1 and was increased to 212 +/- 34% (P < .05) of the value at 15 min-1. Aequorin light emission was lowest at 15 min-1 and was maximally increased at 180 min-1 to 218 +/- 39% (P < .01). In the failing myocardium, average isometric tension was maximum at 60 min-1 (106 +/- 7% of the basal value at 15 min-1, P = NS) and then decreased continuously to 62 +/- 9% of the basal value at 180 min-1 (P < .002). In the failing myocardium, aequorin light emission was highest at 15 min-1. At 180 min-1, it was decreased to 71 +/- 7% of the basal value (P < .01). Including both failing and nonfailing myocardium, there was a close correlation between the frequencies at which aequorin light emission and isometric tension were maximum (r = .92; n = 19; P < .001). Action potential duration decreased similarly with increasing stimulation frequencies in nonfailing and end-stage failing myocardium. Sarcoplasmic reticulum 45Ca2+ uptake, measured in homogenates from the same hearts, was significantly reduced in failing myocardium (3.60 +/- 0.51 versus 1.94 +/- 0.18 (nmol/L).min-1.mg protein-1, P < .005). CONCLUSIONS: These data indicate that the altered force-frequency relation of the failing human myocardium results from disturbed excitation-contraction coupling with decreased calcium cycling at higher rates of stimulation.

Action Potentials↗

PubMed1995

A comparison of surgical and medical therapy for atrial septal defect in adults.

BACKGROUND: The surgical closure of an atrial septal defect is frequently recommended for patients over 40 years of age. However, the prognosis for such patients with unrepaired defects is largely unknown, and the outcome for patients operated on after the fourth decade of life has not yet been compared with that for medically treated patients in a controlled follow-up study. METHODS: In a retrospective study, we examined the clinical course of 179 consecutive patients with isolated atrial septal defects diagnosed after the age of 40. The 84 patients (47 percent) who underwent surgical repair were compared with the 95 patients (53 percent) who were treated medically. The mean (+/-SD) follow-up period was 8.9 +/- 5.2 years (range, 1 to 26). RESULTS: Multivariate analysis revealed that surgical closure of the defect significantly reduced mortality from all causes (relative risk, 0.31; 95 percent confidence interval, 0.11 to 0.85). The adjusted 10-year survival rate of surgically treated patients was 95 percent, as compared with 84 percent for the medically treated patients. In addition, surgical treatment prevented functional deterioration, as measured by the New York Heart Association class (relative risk, 0.21; 95 percent confidence interval, 0.08 to 0.55). However, the incidence of new atrial arrhythmias or of cerebrovascular insults in the two groups was not significantly different. CONCLUSIONS: The surgical repair of an atrial septal defect in patients over 40 years of age, as compared with medical therapy, increases long-term survival and limits the deterioration of function due to heart failure. However, surgically treated patients should be followed closely for the onset of atrial arrhythmias so as to reduce the risk of thromboembolic complications.

Adult↗

PubMed1995

Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy.

BACKGROUND: Previous studies provide considerable evidence that excitation-contraction coupling may be disturbed at the level of the sarcoplasmic reticulum (SR) in the failing human heart. Disturbed SR function may result from altered expression of calcium-handling proteins. METHODS AND RESULTS: Levels of SR proteins involved in calcium release (ryanodine receptor), calcium binding (calsequestrin, calreticulin), and calcium uptake (calcium ATPase, phospholamban) were measured by Western blot analysis in nonfailing human myocardium (n = 7) and in end-stage failing myocardium due to dilated cardiomyopathy (n = 14). The levels of the ryanodine receptor, calsequestrin, and calreticulin were not significantly different in nonfailing and failing human myocardium. Phospholamban protein levels (pentameric form) normalized per total protein were decreased by 18% in the failing myocardium (P < .05). However, phospholamban protein levels were not significantly different in failing and nonfailing myocardium when normalization was performed per calsequestrin. Protein levels of SR calcium ATPase, normalized per total protein or per calsequestrin, were decreased by 41% (P < .001) or 33% (P < .05), respectively, in the failing myocardium. Furthermore, SR calcium ATPase was decreased relative to ryanodine receptor by 37% (P < .05) and relative to phospholamban by 28% (P < .05). CONCLUSIONS: Levels of SR proteins involved in calcium binding and release are unchanged in failing dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium ATPase is decreased relative to its inhibitory protein, phospholamban.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

PubMed1995

Prevalence, characteristics, and risk stratification of electrocardiographic and symptomatic silence of myocardial ischemia despite scintigraphically evidenced ischemia in symptomatic patients presenting with severe coronary artery stenosis.

Symptoms of angina pectoris and transient ST-segment depression are most commonly used to evidence acute myocardial ischemia during exercise testing. However, the diagnostic accuracy of either or both criteria in relation to clinical characteristics and the patient's exercise response has been a subject of controversy. The prevalence and severity of symptoms of angina pectoris and/or ST-segment depression were studied prospectively in 147 consecutive patients with a history of daily angina pectoris, scintigraphic evidence of exercise-induced myocardial ischemia, and coronary artery stenosis > 75%. Logistic regression analysis was applied to determine absence of any or both criteria by the clinical characteristics or exercise response of the patient. During exercise testing, ST-segment response failed to prove scintigraphically evidenced myocardial ischemia in 14/147 patients (10%) and 35/147 patients (24%) when ST-segment depression > or = 0.1 in either > or = 1 or > or = 2 ECG leads was chosen. Symptoms of angina pectoris were found to be absent in 69/147 patients (47%). Only 58 patients (40%) suffered from angina and met the ECG criterion at the time of scintigraphic myocardial ischemia. Absence of ST-segment depression was best predicted by clinical variables such as large myocardial infarction (increase: 2.6 times, p = 0.007), number of stenoses < or = 2 (2.0 times, p = 0.023), and presence of diabetes mellitus (4.3 times, p = 0.035). Painless myocardial ischemia was determined by blood response to exercising. Thus, a double product > 23 increased the risk of painless myocardial ischemia by 1.5 times (p = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗