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H Drexler

Publications and source records attributed to H Drexler.

At least 199 records · Page 11Linked to original sources
PubMed1990

[The role of ACE-inhibition in the therapy of chronic heart insufficiency].

It is now established that ACE-inhibitors are effective in the treatment of severe chronic heart failure; in addition to digitalis and diuretics. Furthermore, recent studies suggest, that beneficial effects of ACE-inhibitors can be expected in patients with moderate heart failure: when combined with diuretics. In atrial fibrillation, the combination with digitalis is recommended. Up to now, there is no clear evidence that monotherapy with ACE-inhibitors is superior to first line therapy with diuretics or digitalis. Nevertheless, initial (and limited) experience favors the use of ACE-inhibitors to prevent progressive LV-dysfunction following myocardial infarction. Based on experimental data, several additional mechanisms of action (besides unloading the heart) have been proposed; which may open up new indications for ACE-inhibition, such as antiarrhythmic, antiischemic or antiproliferative effects (including decreased incidence of coronary restenosis following angioplasty). If confirmed by clinical studies, the indications for ACE-inhibitors will expand considerably, putting emphasis on prevention of occurrence and progression of heart failure rather than treatment of very late stages of chronic heart failure. Yet, the Consensus trial demonstrated a significant impact of these agents on mortality in the latter patient population.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Vasodilatory action of endogenous atrial natriuretic factor in a rat model of chronic heart failure as determined by monoclonal ANF antibody.

Elucidation of the role of (elevated) endogenous atrial natriuretic factor (ANF) in chronic heart failure has been hampered by a lack of specific inhibitors. We used a newly developed monoclonal antibody that has been shown to specifically block both exogenously and endogenously released ANF in vivo. For assessment of the vasodilatory action of ANF in chronic heart failure, either this antibody against ANF or ascites (control serum) was injected in rats with myocardial infarction and failure and in sham animals. Ascites did not alter central hemodynamics in either the sham or infarcted group. Antibody significantly increased right atrial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (SVR) in the infarction group but did not affect these variables in the sham group. Because renal blood flow, as measured by radioactive microspheres, decreased significantly in all four groups, probably due to nonspecific renal vasoconstrictor effects of the ascites, a separate group of infarcted animals was treated with purified ANF antibody (devoid of nonspecific effects) or mouse IgG as a control injection. In these animals, right atrial pressure increased from 1.1 +/- 0.7 to 2.6 +/- 0.7 mm Hg (p less than 0.001). Although SVR, renal blood flow velocity (measured by Doppler probe), and renal vascular resistance did not change in the infarcted animals after administration of purified ANF antibody, a significant correlation was found between baseline plasma ANF values and the change in SVR exerted by purified ANF antibody (r = 0.758, p less than 0.02, n = 9); that is, SVR increased in rats with high baseline plasma ANF (greater than 350 pg/ml), but decreased in animals with plasma ANF less than 200 pg/ml. These results suggest that moderately elevated endogenous plasma ANF levels in chronic heart failure do affect central hemodynamics, primarily by reducing venous pressure (e.g., by decreasing intravascular volume or by venous dilation). Arterial vasodilation, however, appears to emerge when plasma ANF is greatly increased.

Animals↗
PubMed1990

Beta-blocking agents vs. antiarrhythmic interventions in heart failure complicated by arrhythmias.

Approximately 40-50% of the patients with end-stage cardiac failure (either ischemic or nonischemic) die suddenly and unexpectedly, most probably from ventricular fibrillation. It is unclear whether the complex ventricular arrhythmias observed in large numbers of these patients were related to the mode of death. Theoretically, it seems quite reasonable to attempt to suppress the development of life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia or ventricular fibrillation) in those patients. If antiarrhythmic drug therapy is ineffective, alternative antiarrhythmic interventions (antiarrhythmic surgery or implantation of an automatic implantable cardioverter defibrillator) should be considered. In patients with so-called potentially malignant ventricular arrhythmias (e.g., nonsustained ventricular tachycardia), antiarrhythmic drug therapy remains controversial as presently there is no definitive proof that this therapy prolongs life or reduces the incidence of sudden cardiac death. In patients with end-stage cardiac failure, beta-blockade can result in a decrease in resting tachycardia, improvement in clinical heart failure symptoms, and increase in work load capacity. It remains controversial whether treatment with these agents can also improve prognosis and prevent sudden cardiac death. Therefore, at this time, only patients in the earlier stages of this clinical syndrome and with clinical signs of markedly increased sympathetic tone can be treated with low doses of beta-blockers.

Adrenergic beta-Antagonists↗
PubMed1990

[Chronic heart failure: improvement of the prognosis by therapy?].

There are two goals in the management of chronic heart failure: relief of symptoms and prolongation of life. Until recently, pharmacological interventions were tested primarily in order to evaluate their effects on exercise capacity and clinical symptoms. However, two multicenter trials have now provided evidence that treatment of chronic heart failure is able to improve mortality. Indeed, prolongation of life without improving symptoms is not desirable. The two classic keystones of therapy in heart failure, diuretics and digitalis, remain powerful agents to relieve symptoms. However, their impact on survival remains elusive, since no controlled studies are available which address this question with adequate sample size. Vasodilators such as the combination of hydralazine and isosorbide dinitrate and ACE-inhibitors, however, have been shown to improve survival in patients with moderate to severe chronic heart failure. In contrast, prazosin failed to be effective in this respect. More sophisticated questions emerge, in particular, do ACE-inhibitors or vasodilators, effectively interfere with the progression of the disease? May early treatment be preventive and retard the course of heart failure? Several large scale multicenter trials are now under way to address these issues.

Adrenergic beta-Antagonists↗
PubMed1990

Use of inotropes in the critical care setting.

Positive intropic agents are widely used in critical care settings to treat several syndromes associated with hemodynamic derangements. Norepinephrine, epinephrine, dopamine, and dobutamine are the drugs of choice for several specific critical care syndromes, but the properties of each agent and the pathophysiology of the patient are important mediating factors. The hemodynamic status of the patient should be assessed, with invasive hemodynamic monitoring if necessary, and the choice of drug should be made on the basis of data thus obtained.

Amrinone↗
PubMed1990

[Effect of atrial natriuretic factor on coronary vascular tone].

To test whether atrial natriuretic factor (ANF) may be involved in the modulation of coronary vasomotor tone, ANF was injected into angiographically normal left coronary arteries. Measurement of epicardial diameters of the circumflex (Cx) and left anterior descending artery (LAD) were made from biplane angiograms by an automatic contour-detection system. Bolus injection of ANF (0.07 micrograms/kg, diluted in 1 ml 0.9% NaCl, n = 7) increased diameter of proximal segments of LAD (11 +/- 4%) and Cx (10 +/- 4%) (p less than 0.02 each vs control) without altering heart rate and mean arterial pressure (MAP). Intracoronary nitroglycerin (NTG, 0.3 mg) increased diameters of identical LAD and Cx segments by 18 +/- 3% and 20 +/- 4%. Intracoronary ANF infusion (0.02 micrograms/kg/min over 5 min, followed by 0.1 micrograms/kg/min, n = 10) exerted dose-dependent increases in diameters of LAD and Cx (low dose: + 5 +/- 2%, p less than 0.05 vs control; high dose: + 13 +/- 3%, p less than 0.01 vs control). ANF-infusion increased arterial plasma ANF levels from 280 +/- 80 pg/ml during control to 894 +/- 82 pg/ml (low dose; + 614 pg/ml vs control) and to 2290 +/- 228 pg/ml (high dose). Severe ischemia in four patients undergoing angioplasty exerted substantial increase in arterial ANF levels (160 +/- 60 to 608 +/- 111 pg/ml; + 448 pg/ml vs control), similar to the increase elicited by low dose ANF infusion in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1990

[How are tachycardic cardiac arrhythmias modified by therapy of congestive heart failure?].

Previous studies have demonstrated the high prevalence of frequent and complex ventricular arrhythmias in patients with severe congestive heart failure. It has been claimed that these arrhythmias are independent risk factors of prognosis. Moreover in severely depressed left ventricular function frequent and repetitive arrhythmias may deteriorate the hemodynamic situation. Recent clinical studies have drawn increasing attention to the possibility that the desired therapeutic effect of Class I antiarrhythmic agents may be complicated by their ability to aggravate the arrhythmia or to provoke new arrhythmias. These "proarrhythmical effects" were more frequent in patients with life-threatening arrhythmias and in those with severely depressed left ventricular function. Prevention trials with Class I antiarrhythmic agents have failed to show beneficial effects on the arrhythmia profile and on the prognosis of those patients. On the other hand, it is now well recognized that the incidence of cardiac death can be reduced by the use of ACE-inhibitors in this patient population. Accordingly, there is evidence of a reduced incidence of complex ventricular arrhythmias during treatment with these drugs in some of the patients with congestive heart failure. The influence of digitalis on the arrhythmia profile and the cardiac mortality in these patients is still a matter of debate. On the other hand, there is evidence that newer positive inotropic agents such as phosphodiesterase-inhibitors rather increase the number of arrhythmias and the prevalence of sudden cardiac death in this patient population.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium.

The coronary vasomotor response to the cold pressor test was studied with use of quantitative coronary angiography in 32 patients without evidence of coronary artery disease and 55 patients with such disease; in a subset of 22 patients (9 with normal coronary arteries and 13 with coronary artery disease), the effects of the cold pressor test were compared with the effects of the endothelium-dependent vasodilator acetylcholine with simultaneous intracoronary Doppler flow velocity measurements to assess the influence of endothelial dysfunction. The cold pressor test induced vasodilation of 8.9 +/- 5.7% in all 77 analyzed vessel segments of the group with normal arteries (p less than 0.01). In contrast, in patients with coronary artery disease, the 52 analyzed stenotic segments were constricted by -12.1 +/- 9.5% (p less than 0.01), the 57 analyzed vessel segments with luminal irregularities were constricted by -8.9 +/- 5.2% (p less 0.01) and 40 (85%) of 47 angiographically normal segments also were constricted by -7.0 +/- 4.9% (p less than 0.05). Preserved vasodilating capability was demonstrated by intracoronary nitroglycerin in all analyzed segments. In nine patients with normal coronary arteries, the analyzed vessel segments were dilated in response to both the cold pressor test and intracoronary acetylcholine by 10.9 +/- 5.4% and 13.4 +/- 4.7%, respectively. In contrast, in all 13 patients with coronary artery disease, vasoconstriction of identical vessel segments by -9.1 +/- 3.7% and -23 +/- 10.4%, respectively, was observed after both the cold pressor test and intracoronary acetylcholine. Intracoronary propranolol did not significantly affect either the vasodilative response in 11 normal coronary arteries (11.3 +/- 4.4% before and 8.6 +/- 4.3% after beta-blockade) or the vasoconstrictor response in 8 atherosclerotic coronary arteries (-11.4 +/- 4.6% before and -14.6 +/- 5.3% after beta-blockade). The dilation of normal and the constriction of atherosclerotic coronary arteries with cold pressor testing exactly mirror the response to the endothelium-dependent dilator acetylcholine. Endothelial dysfunction in coronary atherosclerosis resulted in a loss of normal dilator function and permitted vasoconstrictor responses to sympathetic stimulation. Thus, coronary vasomotion of large epicardial arteries in response to sympathetic stimulation by the cold pressor test in humans is intimately related to the integrity of endothelial function.

Acetylcholine↗
PubMed1989

Endothelioma cells expressing the polyoma middle T oncogene induce hemangiomas by host cell recruitment.

Mouse endothelioma cells expressing the polyoma middle T oncogene induced hemangiomas in a variety of species such as mice, rats, chicks, and quails. In embryos and newborn mice the hemangiomas expanded within 10-18 hr of injection, disrupting the vasculature and causing the death of the animal. In contrast, the hemangiomas formed a stable structure reminiscent of benign human hemangiomas in adult mice within 5 days. Analysis of the cells comprising the hemangioma revealed that over 95% of the endothelial cells were host derived. No induction of host cell proliferation was detected, and no endothelial mitogens were secreted by the endothelioma cells in vitro. The maintenance of the hemangioma appeared to require the continuous presence of endothelioma cells. The results indicate that these endothelioma cells act as a potent stimulating agent in the rapid formation of hemangiomas by recruiting nonproliferating host endothelial cells.

Animals↗
PubMed1989

Dopexamine in congestive heart failure: how do the pharmacological activities translate into the clinical situation?

Dopexamine is a newly developed sympathetic catecholamine which combines dopaminergic (DA-1) and beta 2-adrenergic agonist activity with only minor beta 1-adrenergic action. Thereby, this compound exerts systemic and preferential renal vasodilation, causing afterload reduction, increases in cardiac output, and improved renal perfusion in animals and normal volunteers. Short-term administration of dopexamine in congestive heart failure established beneficial effects in central hemodynamics, that is, reduction of systemic and pulmonary vascular resistance, combined with a decrease in LV-filling pressures and increased renal blood flow. The effect on central hemodynamics are comparable to sodium nitroprusside. With higher doses, however, heart rate may increase substantially with dopexamine along with increased myocardial oxygen consumption. Experiences with prolonged administration of this drug are scarce and have, so far, yielded conflicting results. Thus, dopexamine appears to be a promising agent in the short-term management of congestive heart failure. However, its ultimate value for prolonged administration remains to be established.

Adrenergic Agonists↗
PubMed1989

Distinct memory impairments following electroconvulsive therapy and imipramine.

Memory functioning was assessed in 26 unmedicated patients with major depressive disorder (DSM-III) who were then administered either bilateral electroconvulsive therapy (ECT) (N = 16) or imipramine 200 mg per day (N = 10). The subjects were retested following seven ECT administrations or 21 days of imipramine treatment respectively. The retrograde memory tasks included recall of public and autobiographic events. The anterograde memory tasks included an immediate memory task, a verbal paired-associates recall task, and a non-verbal figure reproduction task. Depression was significantly improved in the ECT-treated subjects but not in those administered imipramine. Both ECT- and imipramine-treated patients showed a deficit in recent anterograde memory relative to their pretreatment performance, but no deficit in immediate memory. ECT-treated patients also had a significant and well-characterized impairment in retrograde remote memory. By contrast, imipramine-treated patients did not show a retrograde memory impairment which could be explained by treatment. The results suggest qualitatively different memory deficits produced by ECT and imipramine.

Depressive Disorder↗
PubMed1989

Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure. A double-blind, placebo-controlled trial.

To discover the underlying mechanisms involved in the beneficial long-term effects of angiotensin converting enzyme (ACE) inhibitors, we investigated the systemic and peripheral effects of short- and long-term ACE inhibition in patients with chronic heart failure. After assessing the short-term effects and dose titration with cilazapril, a new long-acting ACE inhibitor, 21 patients were randomized to receive either placebo or the ACE inhibitor. Seventeen patients completed the 3-month treatment. Central hemodynamic output, femoral blood flow (measured by thermodilution), oxygen saturation, and lactate and norepinephrine levels were determined simultaneously in the femoral vein and radial artery during treatment and after a 3-month rest and during symptom-limited bicycle exercise. Short-term ACE inhibition improved rest and exercise hemodynamic output, but it did not alter peak femoral blood flow, calculated leg oxygen consumption, or systemic oxygen uptake during exercise, despite significant reduction in femoral norepinephrine extraction and arterial angiotensin levels during exercise. In contrast, long-term ACE inhibition further improved exercise cardiac output and increased leg blood flow (from 2.3 to 2.9 l/min, p less than 0.05), leg oxygen consumption (from 277 to 403 ml/min, p less than 0.05), and systemic oxygen uptake (from 1,133 to 1,453 ml/min, p less than 0.05), whereas these variables remained unchanged with placebo treatment (p less than 0.02 between groups). Moreover, a moderate but significant increase in femoral oxygen extraction occurred after long-term therapy (ACE inhibitor: from 76% to 83%, p less than 0.05; placebo: from 75% to 74%, NS; p less than 0.01 between groups). We conclude that long-term ACE inhibition is clinically beneficial in that it improves blood flow to skeletal muscle during exercise over time. The long-term effects of ACE inhibition are, in part, probably related to peripheral (vascular) mechanisms, for example, by reversing the inability of peripheral vessels to dilate and by improving oxygen utilization.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Atrial natriuretic peptide in a rat model of cardiac failure. Atrial and ventricular mRNA, atrial content, plasma levels, and effect of volume loading.

This study examined the relation between synthesis, atrial storage, and plasma levels of atrial natriuretic peptide (ANP), and it examined plasma ANP levels and hemodynamic output in response to volume expansion in a rat model of myocardial infarction and failure. Arterial ANP concentrations did not correlate linearly with infarct size, but they did show an abrupt increase when infarct size exceeded 30% of the left ventricle, similar to the abrupt increase of left ventricular end-diastolic pressure with infarct size greater than 30%. Consequently, a close relation was found between plasma ANP levels and left ventricular end-diastolic pressure (n = 23, r = 0.89, p less than 0.001). Atrial ANP content per gram of tissue but not ANP content per pair of atria was reduced in rats with large infarcts (greater than 40%, p less than 0.05 vs. control animals). ANP mRNA level per pair of atria (related to total atrial RNA), determined by liquid hybridization (controlled by northern blot analysis), was increased by 38% in infarcted rats (p less than 0.05 vs. controls), but the ratio of atrial ANP mRNA relative to atrial beta-actin mRNA levels was not increased. Right and left ventricular ANP mRNA level increased by 90% and 380%, respectively, far exceeding the concomitant increase in beta-actin mRNA (+26% in the left ventricle). Plasma ANP increased with volume loading in controls and rats with moderate infarcts but not in rats with large infarcts despite a similar increase in right atrial pressure (compared with control animals); thus, the relation of delta ANP/delta right atrial pressure exerted by volume loading decreased in rats with large infarcts. Similarly, the response of cardiac output and renal blood flow (determined by radioactive microspheres) to volume loading was attenuated in rats with large infarcts. Thus, in this model of chronic cardiac failure, the activation of the ANP system is closely coupled with the increase in intracardiac pressures without correlating linearly to the extent of myocardial loss. Second, in severe cardiac failure, additional stimulation such as volume loading may elicit only an attenuated ANP secretion response, for example, due to saturation of the ANP receptor sensing system or to a limited transformation rate of pro-ANP. Third, the increase in atrial ANP synthesis and the increase in atrial ANP gene expression seems limited; however, substantial specific ANP gene expression occurs in the ventricles, which, in turn, may contribute to increased plasma ANP levels in chronic heart failure.

Animals↗
PubMed1989

Flow-dependent coronary artery dilatation in humans.

To determine the role of endothelium-mediated flow-dependent coronary dilatation in humans, we studied the coronary dilatation exerted by maximal pharmacologic increase of coronary flow in 14 patients with normal coronary arteries. Biplane views of the circumflex (Cx) and left anterior descending (LAD) coronary arteries were obtained before and 80 seconds after inducing a maximal increase in flow selectively in the Cx by injecting 7 mg papaverine through a 2F infusion catheter in the midportion of the Cx (n = 10). The diameter of the proximal Cx segment (exposed to increased flow but not to papaverine directly) increased with papaverine by 11.1 +/- 4% (range, 5.2-16.4%, p less than 0.001 vs. control), whereas the LAD diameter did not change. LAD and Cx diameters increased by 18.3% and 21.2% after nitroglycerin given into the left main artery, which showed the preserved capability of the LAD to dilate. In four patients with normal coronary arteries and six patients with coronary artery disease (CAD, non-flow-limiting stenosis), a similar protocol was applied with the LAD for the assessment of flow-dependent dilatation. Simultaneously, intracoronary blood flow velocity was measured by an intracoronary Doppler catheter. Papaverine-induced coronary flow reserve (peak/resting velocity ratio) in the LAD was 4 +/- 0.7 (range, 3.5-5) in normal arteries and was 3.5 +/- 0.6 (range, 2.7-4.4) in CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Skeletal muscle blood flow, metabolism and morphology in chronic congestive heart failure and effects of short- and long-term angiotensin-converting enzyme inhibition.

Blood flow to skeletal muscle during exercise is limited in patients with chronic congestive heart failure compared with normal persons. This may, in part, be attributed to the inability of the vessels to dilate adequately. In addition, an abnormal skeletal muscle metabolism with oxidative capacity can be demonstrated in patients with chronic congestive heart failure. The latter may partially explain why vasodilators and inotropes that improve central hemodynamics, global leg perfusion or skeletal muscle blood flow during exercise do not increase oxygen uptake by working muscle after acute drug administration. Furthermore, increases in blood flow to skeletal muscle may be redistributed to inactive or less oxygen-dependent muscle fibers. Although acute angiotensin-converting enzyme inhibition usually neither exerts substantial improvement in exercise hemodynamics nor interferes with leg perfusion during exercise, skeletal muscle blood flow and oxygen uptake gradually increases with long-term angiotensin-converting enzyme therapy, leading to improved systemic oxygen consumption and exercise tolerance. Several factors, such as reduction in plasma and vascular angiotensin II and sympathetic nervous activity, increased prostaglandin levels and renal function may contribute to this beneficial long-term effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Transcription stimulates recombination. I. Specialized transduction of Escherichia coli by lambda trp phages.

Specialized transduction of Trp+ by lambda trp phages, whose trp genes were totally under the control of the PL promoter of lambda, was studied. In all cases the efficiency of transduction (EOT) was significantly reduced in homoimmune recipients. In Su- recipients the EOT by phages whose trp gene expression was N-dependent was reduced 2- to 3-fold by the lambda mutant Pam but 30- to 100-fold by an Nam mutant. With phages whose trp gene expression was N-independent, either Pam or Nam caused 2- to 3-fold reduction in the EOT. It was concluded that transcription of the trp genes of the specialized transducing phages had a direct, stimulatory effect on their recombination leading to transduction.

Bacteriophage lambda↗