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Biomedical subjects

H Just

Publications and source records attributed to H Just.

At least 163 records · Page 9Linked to original sources
PubMed1992

Alterations of skeletal muscle in chronic heart failure.

BACKGROUND: The present study was designed to define the prevalence and characteristics of skeletal muscle alterations in patients with chronic heart failure (CHF) and their relation to exercise capacity. METHODS AND RESULTS: The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry in 57 patients with CHF and 18 healthy controls. The volume density of mitochondria (Vvm) and the surface density (Svmc) of mitochondrial cristae were evaluated as a structural correlate of oxidative capacity of skeletal muscle. Vvm and Svmc were reduced by approximately 20% in patients with severe CHF irrespective of age and etiology. The cytochrome oxidase activity in mitochondria as determined by cytochemistry and subsequent morphometry in a subset of patients (n = 10) was significantly decreased in heart failure (p less than 0.01). The capillary length density of skeletal muscle was reduced in CHF (n = 12, p less than 0.05), and the fiber type distribution was shifted to type II fibers (n = 15, p less than 0.05). Vvm and Svmc were significantly related to peak exercise VO2 (r = 0.56, p less than 0.001, n = 60) and to VO2 at anaerobic threshold (r = 0.535, p less than 0.0001, n = 60). In 16 patients with severe heart failure, Vvm was inversely related to the duration of heart failure (r = 0.545, p less than 0.03). In 11 patients who underwent repeat biopsies after 4 months, a correlation was observed between the change in Vvm and the change in peak exercise VO2 (r = 0.89, p less than 0.001). CONCLUSIONS: These findings indicate that patients with CHF develop significant ultrastructural abnormalities of skeletal muscle reflecting a depressed oxidative capacity of working muscle. It appears that these alterations of skeletal muscle contribute to the decreased exercise capacity of these patients but are, in principle, reversible by an effective treatment regimen.

Aging↗
PubMed1992

Prevalence of circadian variations and spontaneous variability of cardiac disorders and ECG changes suggestive of myocardial ischemia in systemic arterial hypertension.

BACKGROUND: Systemic hypertension is a well-known risk factor for coronary artery disease and sudden cardiac death. Recent interest focused on the presence of malignant ventricular arrhythmias (VA) and myocardial ischemia in hypertensive patients and provided a potential link for fatal tachyarrhythmic events. METHODS AND RESULTS: We studied 150 untreated normokalemic hypertensive patients (56 +/- 9 years; 56 women and 94 men) without manifest coronary artery disease to determine prevalence, severity, and interaction of VA and significant ST segment changes induced by daily activities. One third of the patients were randomized to 4 weeks of placebo and restudied for spontaneous variability of the two parameters. All patients were included in a 3-year follow-up study. VA were observed in 129 of 150 hypertensive patients (86%) and peaked in the early morning and late afternoon. Twenty-two patients (15%) had ventricular pairs, and 20 patients (13%) had nonsustained ventricular tachycardia. Transient ST segment depression observed in 47 patients (33%; mean incidence, 2.7 +/- 0.8 episodes/24 hr) showed a characteristic circadian variation similar to VA and were asymptomatic in 93% of the episodes. At the time of transient ST segment depression, VA increased 4.6 times (p less than 0.01). After 4 weeks of placebo, marked variations in the incidence of VA (VA suppression rate -100%, or increase greater than 400%) were observed in 29% of the patients, and in 60% of all patients repetitive VA were present in only one of the two Holter recordings. Day-and-night variations of VA and transient ST segment changes were highly reproducible during the placebo period. After 3 years of follow-up, eight of 146 patients (5%) had suffered myocardial infarction, and five patients had died from cardiac events (three patients died from sudden cardiac death). Logistic regression analysis revealed left ventricular hypertrophy (relative risk, 6.1; p less than 0.01) and transient ST segment abnormalities during daily activities (relative risk, 4.4; p less than 0.05) to be of independent prognostic significance to predict cardiac events during follow-up instead of repetitive VA (relative risk, 1.3; NS). CONCLUSIONS: VA associated with a high spontaneous variability and predominantly asymptomatic transient ST segment changes are common in hypertensives; the interaction of both risk factors may provide an important link for fatal VA. Antiarrhythmic therapy is not to be recommended in the majority of patients. Presence of left ventricular hypertrophy and transient ST segment changes were the most powerful predictors of cardiac events during the follow-up.

Adult↗
PubMed1992

Mechanisms of interaction between the sulfhydryl precursor L-methionine and glyceryl trinitrate.

BACKGROUND: L-Methionine potentiates systemic hemodynamic effects of intravenous glyceryl trinitrate (GTN) in tolerant and nontolerant patients to a similar extent as N-acetylcysteine (NAC). This potentiation of GTN action by L-methionine has been attributed to enhanced intracellular formation of nitrosothiols, known to be potent stimulators of soluble guanylyl cyclase. This study was performed to analyze directly the effects of L-methionine on GTN-induced dilation of large epicardial arteries and the venous capacitance system of the dog in the tolerant and nontolerant states. Cultured rat aortic vascular smooth muscle cells and purified guanylyl cyclase were used to study potential intracellular and extracellular mechanisms responsible for this interaction. METHODS AND RESULTS: In awake nontolerant dogs, L-methionine (100 mg/kg) potentiated the tachycardic response to GTN (5.0 and 15 micrograms/kg/min) and enhanced the hypotensive action of GTN (1.5 and 5.0 micrograms/kg/min) in anesthetized, nonreflexic dogs. In nontolerant and tolerant dogs, however, L-methionine did not alter the dose-response of large epicardial artery dilation to intravenous GTN challenges and did not modify nitrate tolerance of the low pressure system of the dog. The infusion of L-methionine (100 mg/kg) significantly increased plasma methionine levels (from 52 +/- 12 to 1,141 +/- 239 microM), cystine levels (from 12 +/- 4 to 26 +/- 7 microM), but not homocystine levels. In vitro, the L-methionine conversion product L-cysteine (0.1-1.0 mM) but not homocysteine significantly enhanced the augmentation of purified guanylyl cyclase activity by GTN (100 microM). Incubation of cultured rat aortic smooth muscle cells with L-methionine (10 microM or 1 mM) did not result in a significant increase of free intracellular sulfhydryl group content. CONCLUSIONS: The L-methionine conversion product L-cysteine mediates tolerance independent the potentiation of GTN action. This may result from an L-cysteine-induced formation of a vasoactive metabolite of GTN (nitric oxide) or nitrosothiol. This effect occurs primarily in the resistance vessel circulation, not in large epicardial arteries and veins. The lack of effect of L-methionine on sulfhydryl group content in large conductance vessels indicates that hepatic L-methionine metabolism constitutes the significant source of L-cysteine. These findings strongly suggest that administration of sulfhydryl-group precursor L-methionine does not represent a therapeutic alternative to a nitrate-free interval to restore nitrate sensitivity in tolerant large epicardial arteries and veins.

Animals↗
PubMed1992

Neurohormonal inhibition and hemodynamic unloading during prolonged inhibition of ANF degradation in patients with severe chronic heart failure.

BACKGROUND: The purpose of this study was to investigate the therapeutic potential of prolonged inhibition of atrial natriuretic factor (ANF) degradation in patients with severe chronic heart failure. METHODS AND RESULTS: The effects of repeated doses of the endopeptidase inhibitor candoxatrilat (150 mg i.v.) were examined over a 24-hour period in patients with severe chronic heart failure (New York Heart Association class III-IV). Plasma alpha-hANF(99-126) was elevated at baseline (235 +/- 59 pg/ml), increased 2.5-fold at 2 hours after the first dose, and remained significantly elevated throughout the 24-hour protocol. In contrast, pro-hANF(31-67) decreased from 3,151 +/- 616 to 2,072 +/- 362 pg/ml (p less than 0.05). Cardiac index (CI) increased only transiently after the first dose of candoxatrilat (CI, 2.11 +/- 0.2 to 2.67 +/- 0.28 l/min/m2, p less than 0.05). Sodium excretion increased sixfold (p less than 0.05) 2 hours after the first dose of candoxatrilat and remained significantly elevated throughout the protocol. Degree of natriuresis and diuresis in response to candoxatrilat was closely related to baseline cardiac output. Glomerular filtration rate and volume excretion did not change significantly. Pulmonary capillary wedge pressure fell from 23 +/- 3 to 18 +/- 3 mm Hg (p less than 0.05) and remained below baseline throughout the 24 hours. Arterial pressure, heart rate, and total peripheral resistance did not change significantly during the 24-hour period. Urinary cGMP excretion increased fivefold (p less than 0.05), whereas urinary ANF immunoreactivity and plasma cGMP levels remained unchanged. Excretion of prostacyclin metabolite 6-keto-PGF-1 alpha increased 3.3-fold (p less than 0.05). Plasma norepinephrine and epinephrine levels decreased significantly after candoxatrilat and remained suppressed over the 24-hour period. There was also a transient reduction in plasma vasopressin, aldosterone levels, and plasma renin activity. Hematocrit, total protein content, and plasma albumin concentrations did not change, indicating that no fluid shift into the extravascular space had occurred. CONCLUSIONS: 1) The inhibition of ANF degradation causes sustained drop in left and right atrial pressures that appears to be mediated by an inhibition of neurohumoral activity; 2) concomitant inhibition of bradykinin breakdown (which in turn stimulates renal prostacyclin synthesis) contributes to natriuresis; 3) the close correlation between renal response and baseline cardiac index indicates that an inadequate renal perfusion secondary to low cardiac output diminishes the efficacy of this treatment modality. This spectrum of action would be advantageous for a first-line diuretic agent early in the course of disease rather than in patients with advanced chronic heart failure.

Aged↗
PubMed1992

Efficacy of intravenously administered amiodarone for short-term control of serious arrhythmias.

Intravenously administered amiodarone exerts substantial antiarrhythmic activity that is based on several different electrophysiologic mechanisms. Of these, the most important consists of an antitachycardic effect together with a significant prolongation of repolarization. The acute intravenous administration of amiodarone has been found to be effective in supraventricular and ventricular tachyarrhythmias resistant to conventional antiarrhythmic agents. Because amiodarone is free of detrimental hemodynamic effects in the majority of patients, intravenous administration of this compound seems to be particularly suitable in patients with serious arrhythmias in the setting of compromised left ventricular function.

Action Potentials↗
PubMed1992

Exercise-induced symptomatic and asymptomatic myocardial ischemia in patients with severe coronary artery disease: focus on the efficacy and safety of gallopamil.

Symptomatic and asymptomatic episodes of transient myocardial ischemia are well-known risk factors in patients with coronary artery disease. In a single-blind, randomized, and placebo-controlled study, the efficacy and safety of gallopamil was studied during a 1-week treatment period in 25 patients with high-grade coronary artery stenosis and frequent, exercise-induced episodes of myocardial ischemia. Eighteen patients were men, and seven patients were women; the mean age +/- SD was 59 +/- 7 years. After a 1-week run-in period (days 1-7), all patients were treated with gallopamil 50 mg t.i.d. (days 8-14) and placebo t.i.d. (days 15-21) or vice versa. Twenty-four-hour Holter monitoring, exercise testing, and adverse effects were controlled at days 7, 14, and 21. During the run-in period, all patients suffered a mean of 5.9 +/- 2.9 episodes of transient myocardial ischemia, mean ischemic duration was 38 +/- 29 min/day. Gallopamil increased exercise tolerance from 7.9 to 9.8 min (+24%, p < 0.05) and resulted in reduction of the weekly usage of short-acting nitrates by 45% compared to placebo. During 24-h Holter monitoring, mean heart rate at the onset of ST-segment depression increased from 106 to 118 beats/min (p < 0.05). The frequency of daily ischemic episodes was reduced after gallopamil administration from 6.1 to 3.9 episodes/day (-37%, p < 0.05), the total ischemic burden decreased for symptomatic episodes by -54% (p < 0.05) and for asymptomatic episodes by 29% (p < 0.05). Gallopamil modified the circadian distribution of ischemic episodes by modifying the morning peak of transient myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Arterial dilatory reserve in congestive heart failure.

AIM: The purpose of this study was to determine whether there are abnormalities in flow-mediated large vessel relaxation in patients with congestive heart failure (CHF). METHODS: The radial arterial diameter and flow responses upon the release of 10 min of forearm arterial occlusion (reactive hyperemia) were measured with ultrasound and Doppler devices. RESULTS: In patients with CHF there was a 26% reduction in peak blood flow (P = 0.09) compared to age-matched controls. However, the increase in arterial diameter that followed the peak blood flow was reduced by 49% in CHF (P < 0.01). CONCLUSIONS: The causes of the abnormal flow-mediated large artery relaxation in CHF are unclear; both structural and endothelial abnormalities may contribute.

Blood Flow Velocity↗
PubMed1992

[Risk stratification and long-term therapy with amiodarone in patients with idiopathic dilated cardiomyopathy].

Patients with cardiomyopathy are known to suffer from a high prevalence of tachyarrhythmic complications and sudden cardiac death. In a prospective study, 30 patients (25 men, 5 women, mean age: 52 +/- 12 years) with dilated cardiomyopathy underwent 48-h-Holter monitoring and programmed electrical stimulation and, independent from the results of the diagnostic work-up, were then randomized either to amiodarone or to a conventional or no antiarrhythmic therapy. At baseline, frequent ventricular arrhythmias (> 30 ventricular premature beats/h) were observed in 15/30 patients (50%), 13 patients (43%) had repetitive ventricular arrhythmias, additionally. Four patients suffered spontaneous sustained tachyarrhythmias. During programmed electrical stimulation, sustained monomorphic ventricular tachycardia was induced in 3/3 patients with and in 1/25 patients (4%) without a history of sustained tachycardia. Sustained monomorphic ventricular tachycardia was induced with one to two extrastimuli; three extrastimuli only increased the incidence of inducible ventricular fibrillation (8 patients, 28%). During a mean follow-up of 28 +/- 6 months 10/30 patients (33%) died for cardiac reasons (sudden cardiac death: 4/10 patients). Cardiac death was most likely in patients with a left-ventricular ejection fraction < 35% (5/18 patients, 28% versus 1/12 patients with ejection fraction > 35%, 8%) and further increased in the presence of reduced exercise tolerance and frequent and repetitive ventricular arrhythmias (4/7 patients, 57%). In the amiodarone group 4/15 patients died (27%, sudden cardiac death: one patient), while in patients not treated by amiodarone 8/15 patients died (54%; sudden cardiac death: three patients). Amiodarone therapy was well tolerated in all but one patient.

Adult↗
PubMed1991

Time course and interrelation of reperfusion-induced ST changes and ventricular arrhythmias in acute myocardial infarction.

With the increasing use of thrombolytic therapy, the presence and time course of reperfusion-induced ventricular arrhythmias and ST-segment changes have become of particular interest. Technical improvements in bipolar Holter monitoring offer the opportunity to record both parameters continuously and simultaneously. Time course and interaction of both parameters in dependence on the onset of thrombolysis and time of reperfusion were investigated in 30 patients with acute myocardial infarction. Reperfusion was achieved in 20 patients after 49 +/- 23 minutes and in another 2 patients after 120 minutes (73%, group A). Vascular occlusion persisted in 8 patients for greater than 24 hours (group B). Sudden ST-segment changes (greater than 0.2 mV/15 min) in the bipolar leads indicated reperfusion in 7 of 22 patients (32%). Idioventricular rhythms, most frequent in reperfused patients (group A: 18 of 22 patients, mean 121 beats/hour), were unspecific reperfusion markers (group B: 5 of 8 patients, 1 beat/hour) unless frequent (p less than 0.05) or longer lasting, repetitive (p less than 0.01) episodes were considered. Premature ventricular beats and couplets (p less than 0.05) were also most frequent in group A (peak frequency 3 to 5 hours after thrombolysis). Ventricular tachycardia observed in 21 of 22 patients (95%) in group A and in 3 of 8 (38%) in group B (p less than 0.01) attained their peak frequency 7 to 9 hours after thrombolysis. They occurred most often in anterior myocardial infarction and were often preceded by frequent singular premature beats (r = 0.78).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The natural course of atrial septal defect in adults--a still unsettled issue.

Atrial septal defect is the most frequently encountered major congenital cardiac disorder in the adult population, with a prevalence of 0.2 to 0.7 per thousand. Several patients tolerate large unrepaired defects for 80 years or even longer without serious disability. However, it is assumed that, as a rule, atrial septal defect reduces life expectancy, the average age at death not exceeding 50 years. This estimation is based on studies derived mainly from necropsy series or from the admission profile of patients undergoing late operative repair. The onset of atrial fibrillation, with an incidence ranging from 13 to 52 percent among patients older than 40 years, as well as the progression of pulmonary arterial hypertension in up to 53 percent of patients, results in congestive heart failure and functional limitation. On the other hand, very few longitudinal studies thus far have directly and systematically followed the course of adults with unrepaired defects. Thus, many issues regarding the natural history and prognosis of atrial septal defect still remain unresolved. Follow-up series of older patients with nonoperated defects could yield valuable information even in an era when routine early surgical closure is increasingly being recommended.

Adult↗
PubMed1991

Usefulness of esmolol in unstable angina pectoris. European Esmolol Study Group.

Esmolol is a new cardioselective beta blocker with unique pharmacokinetic properties resulting in a half-life of only 9 minutes. The present multicenter, randomized, placebo-controlled study examined the hemodynamic and antiischemic effects of this compound given as an adjunctive to conventional medical therapy in 113 patients with unstable angina. Fifty-nine patients received esmolol and 54 received matching placebo infusions. Esmolol was titrated in a step-wise manner at dosages of 2 to 24 mg/min until a 25% reduction in the double product was achieved; thereafter, esmolol was continuously infused for up to 72 hours. Esmolol caused a significant and persistent decline in heart rate and blood pressure throughout the entire study period. Clinical events, such as development of acute myocardial infarction or the need for urgent revascularization, occurred in 3 esmolol compared with 9 placebo patients (p = 0.06). There was also a trend toward reduction of silent ischemia as judged by Holter monitoring (mean [+/- standard deviation] duration/patient/24 hours, 21 +/- 81 minutes in the esmolol and 35 +/- 128 minutes in the placebo groups). Esmolol-related adverse effects were mostly cardiovascular in origin and could be managed promptly by downward dose titration or cessation of drug infusion. Thus, esmolol appears to be a safe and effective drug for patients with unstable angina because it permits a large degree of flexibility in adapting the desired level of beta blockade to the patient's changing clinical presentation.

Adrenergic beta-Antagonists↗
PubMed1991

Peripheral adaptations in congestive heart failure: a review.

In congestive heart failure, peripheral adaptive mechanisms play a significant and largely underestimated role. In acute heart failure, sympathetic-mediated peripheral vasoconstriction together with chronotropic and inotropic actions serves to maintain perfusion pressure and blood supply to the vital organs. In chronic heart failure, activation of the renin-angiotensin system increases peripheral vascular resistance and arterial tone and decreases arterial compliance and vasodilator capacity. Endothelium-mediated, flow-dependent vasodilation is reduced as a consequence of reduced blood flow. Deconditioning renders the blood vessels incapable of dilating in response to increased flow. Simultaneously, reduced blood flow and inactivity are induced by deconditioning, with functional and structural consequences within the skeletal muscle. Exercise performance is limited by reduced overall blood flow, reduced conductance of the feeding arteries, elevated tone of the resistance vessels, reduced vasodilator capacity, impaired dissipation of heat from the working muscle, and functional and structural changes of the skeletal muscle due to underperfusion and inactivity. The adaptive mechanisms operate at different time scales. Under therapeutic intervention, their reversibility also follows different time constants. Restoration of the vasodilator capacity of the large arteries and of the abnormalities of skeletal muscle in heart failure requires time. Vasodilation with reduced pre- and/or afterload will retard progression of the superimposed ventricular dilation and hypertrophy, and therefore retard the progress of the disease. However, restoration of the peripheral blood flow and of organ function will require time. Restoration of the vascular compliance and of the full amplitude of adaptive flow-dependent vasodilation in the large arteries requires weeks or months. Similarly, restoration of functionally and morphologically altered skeletal muscle can be expected to be reversible over a longer time period.

Blood Circulation↗
PubMed1991

Adaptive changes in the periphery and their therapeutic consequences.

Systemic vasoconstriction in chronic heart failure is due to several compensatory mechanisms with different time courses. Peripheral vasoconstriction mediated by increased sympathetic tone and activation of the plasma renin-angiotensin system may act primarily for short-term control. The effects of the vascular renin-angiotensin system, impaired flow-dependent, endothelium-mediated dilation (resulting from chronically reduced flow) and structural alterations of the vessel wall slowly emerge with time. In addition, fluid retention may contribute to increased vascular stiffness in chronic heart failure. Improved cardiac output with acute administration of vasodilators and inotropes is not immediately translated into increased blood flow to skeletal muscle, because (1) the reversal of the peripheral alterations described develops slowly over time (in fact, vasodilators and inotropes given acutely may cause redistribution of blood flow in skeletal muscle without improving oxygen availability); and (2) intrinsic abnormalities of skeletal muscle exist in chronic heart failure (e.g., due to chronic deconditioning, resulting in reduced oxidative capacity of skeletal muscle, as suggested by ultrastructural analysis and nuclear magnetic resonance spectroscopy). Drugs that interfere with the underlying compensatory mechanisms (e.g., renin-angiotensin system) without development of tolerance during long-term therapy exert beneficial effects after long-term treatment (e.g., the beneficial effects of angiotensin-converting enzyme inhibitors are, in part, due to peripheral mechanisms--the inability of the peripheral vessels to dilate--and to improvement of peripheral oxygen extraction).

Adaptation, Physiological↗
PubMed1991

Clinical and Doppler echocardiographic follow-up after percutaneous balloon valvuloplasty for aortic valve stenosis.

Percutaneous balloon valvuloplasty has been shown to increase the aortic orifice area and to improve clinical symptoms. However, there are only few data concerning long-term results after balloon valvuloplasty. In this study, 36 patients (11 men, 25 women, mean age 75 +/- 8 years) were followed after balloon valvuloplasty for a period of up to 18 months by means of clinical parameters and repeated Doppler echocardiographic measurements after 1, 3, 6, 12 and 18 months. Invasive measurements revealed a decrease of the systolic peak gradient from 78 +/- 24 to 38 +/- 13 mm Hg (p less than 0.001), and an increase in the aortic orifice area from 0.58 +/- 0.23 to 0.93 +/- 0.2 cm2 (p less than 0.001). The Doppler echocardiographic approach revealed that the maximal instantaneous gradient decreased from 96 +/- 26 to 67 +/- 22 mm Hg (p less than 0.001). The aortic orifice area increased from 0.49 +/- 0.16 to 0.73 +/- 0.21 cm2 (p less than 0.001). Three patients (8%) died in the hospital. After hospital discharge, 16 patients (44%) died and 8 patients (22%) underwent successful aortic valve replacement after a mean follow-up of 8 +/- 6 months. Nine patients (25%) were alive after a follow-up period of 18 months. Seven of these (19%) remained clinically improved. During follow-up, the Doppler echocardiographic results revealed a continuous trend toward the preprocedural severity of the aortic valve stenosis. Progression of restenosis assessed by Doppler echocardiographic measurements was accelerated in the group of patients who subsequently died or underwent repeat balloon valvuloplasty or aortic valve replacement.

Aged↗
PubMed1991

[Prolongation of hospital stay by nosocomial pneumonia and wound infection].

From June 1988 to September 1989, a prospective survey comprising a total of 1183 patients in a university hospital was carried out to ascertain the additional length of stay in intensive care units because of nosocomial pneumonia associated with artificial ventilation (418 patients, 296 men, 122 women, mean age 48.8 +/- 21 years, ventilated for more than 24 h) or by postoperative wound infections (765 patients, 501 men, 264 women, mean age 60 +/- 11 years, after operations on the large bowel, heart or biliary tract). Each patient with a nosocomial infection was matched against a variable number of control patients (for cases of pneumonia a maximum of 6, for wound infections a maximum of 10) without nosocomial infection. Pneumonia developed in 100 (23.9%) of artificially ventilated patients, and 46 of these patients together with 101 controls were entered into the matching procedure. 24 patients with pneumonia had to be excluded from analysis because no controls could be found for them, and also 30 patients who died while in the intensive care unit. 49 (6.4%) of the surgical patients contracted postoperative wound infections. 43 of them, together with 210 controls, were entered into the matching procedure. Among patients with pneumonia the average additional duration of stay was 11.5 days, and among patients with post-operative wound infections it was 13.9 days. The results confirm that nosocomial infections contribute substantially to prolongation of hospital stay and hence to the costs.

Adult↗