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Biomedical subjects

D Magometschnigg

Publications and source records attributed to D Magometschnigg.

At least 37 records · Page 2Linked to original sources

Arterial baroreflex sensitivity and blood pressure variabilities before and after carotid surgery.

Carotid surgery is frequently associated with postoperative blood pressure alterations. The role of baroreceptors with regard to these alterations was assessed in 50 patients by determining the pre- and postoperative mechanoreceptor sensitivity after Valsalva maneuver and intravenous injections of angiotensin and nitroglycerine as described by Smyth, Sleight and Pickering. In addition, blood pressure was monitored perioperatively and renin and aldosterone levels were measured. In patients with arterial hypertension a postoperative increase of receptor reactivity can be seen necessitating a reduction of antihypertensive therapy in more than 50% of cases. In normotensive patients no uniform response can be observed. A possible explanation for this effect might be the local increase of pressure in the operated vascular segment. The postoperative reintegration of receptor areas which had been adjusted to a reduced pressure level might induce a more sensitive response than can be seen for the remaining receptors, which usually are less responsive in hypertensive patients.

Aged↗

A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension.

The aim of this 3-month double-blind multicenter trial was to compare the antihypertensive efficacy and tolerability of the ACE inhibitor perindopril with those of a diuretic combination. After 1 month of receiving placebo, 165 patients with essential hypertension were randomised to perindopril 4 mg (n = 82) or to 50 mg hydrochlorothiazide + 5 mg amiloride (n = 83). The patients were treated for 3 months with monthly assessments, "uncontrolled" patients (DBP greater than 90 mm Hg) had their dosage doubled and then, if necessary, atenolol 50 mg was added. At the end of the 3-month study, mean decreases in supine and standing systolic and diastolic blood pressures were similar in both groups. In the perindopril group, BP control was obtained in 56% of the patients with the 4 mg dosage and required an increase to 8 mg alone in 16% and with atenolol in 5%. The corresponding percentages in the diuretic group were 48, 23 and 13%. The overall percentage of "controlled" patients was similar in the 2 groups, respectively 78 and 84%. The nature and incidence of complaints were comparable in the 2 groups. Adverse laboratory changes were more frequent in the diuretic group: decrease in blood sodium (140.5 vs 139.1 mmol/l; P less than 0.01), potassium (4.2 vs 3.9 mmol/l; P less than 0.01) with 10 patients having significant hypokalemia, increase in blood urea, triglycerides and uric acid. By contrast, a transient increase in blood potassium with a decrease in triglycerides was observed in the perindopril group.

Adolescent↗

Differential therapy with calcium antagonists in pulmonary hypertension secondary to COPD. Hemodynamic effects of nifedipine, diltiazem, and verapamil.

In 53 patients with COPD and precapillary pulmonary hypertension, we investigated the effect of three typical calcium antagonists on hemodynamics at rest and during bicycle ergometer exercise. In the responders, the decrease in pulmonary vascular resistance following nifedipine was 23 percent at rest (p less than 0.0005) and 35 percent during exercise (p less than 0.0005); following diltiazem, it was 10 percent at rest (p less than 0.05) and 23 percent during exercise (p less than 0.025); following verapamil, it was 22 percent at rest (p less than 0.005) and 11 percent during exercise (p less than 0.025). The cardiac index rose significantly at rest and under exercise only after the administration of nifedipine (+16 percent and +8 percent, resp). Nifedipine caused the most distinctive peripheral vasodilation. The heart rate increased slightly following nifedipine and decreased slightly following diltiazem and verapamil. After long-term therapy with nifedipine (13 +/- 5 months), the decrease in pulmonary artery pressure and pulmonary vascular resistance was no longer significant. In our opinion, the different hemodynamic action profiles will have consequences for the differential therapy in patients with COPD and pulmonary hypertension.

Calcium Channel Blockers↗

The effect of concomitantly administered antacids on the bioavailability of lornoxicam, a novel highly potent NSAID.

Antacids are used in the treatment of upper gastrointestinal side-effects during therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Since pharmacokinetic interactions between antacids and NSAIDs have been reported, it was investigated whether aluminium and magnesium hydroxide (Maalox as oral suspension) or aluminium hydroxide and calcium carbonate (Solugastril as oral gel) influenced the bioavailability of Lornoxicam (rINN), a new potent NSAID from the chemical group of the oxicams. Eighteen male volunteers were given 4 mg of Lornoxicam as a film-coated tablet either alone or together with 10 ml of Maalox or 10 g of Solugastril in an open, randomized, three-way cross-over study. The levels of Lornoxicam in plasma were determined by HPLC following solid-phase extraction. It was found that none of the antacids changed significantly any of the following pharmacokinetic parameters: elimination half-life (t1/2 beta), concentration at peak time (Cmax), time to reach the peak (tmax) and area under the curve to infinity (AUCo-infinity). The results indicate that the concomitant administration of antacids did not influence the pharmacokinetic profile of Lornoxicam. Furthermore they confirm the short elimination half-life of Lornoxicam in man, which is markedly shorter than that of other oxicam-type compounds.

Adult↗

[Value of indirect 24-hour blood pressure determination and blood pressure self-control for the diagnosis of arterial hypertension].

For judgement of hypertension 24-hours-blood pressure readings and self recorded blood pressures are new, more sensitive techniques which help us to recognize patients with elevated cuff blood pressures who do not need drug-treatment. Furthermore these techniques help us to select those patients who are in need of treatment as well as to adjust the treatment more adequately to the patients real blood pressure. These new tools in judgement and treatment of hypertension help us to treat our patients with more safety and less side effects. Therefore we should force this new way of hypertension judgement.

Blood Pressure↗

Cardioselectivity of cetamolol compared with atenolol and nadolol.

The selectivity of the beta-adrenoceptor blockade produced by single oral doses of cetamolol, atenolol, and nadolol was compared in normal male subjects. Study 1 established the dose at which each drug provides equivalent beta-1 blockade. Beta-1 blockade was estimated using the degree of inhibition of the increased heart rate (HR) response to graded exercise. Cetamolol (30 mg), atenolol (100 mg), and nadolol (80 mg) all attenuated the HR response to a comparable extent. This result established that the dose ratio of cetamolol:atenolol:nadolol of 1.00:3.33:2.67 provides equipotent beta-1 blockade. This ratio of doses was used in Studies 2 and 3 to evaluate the antagonism of beta-2-mediated responses to titrated doses of intravenous isoproterenol (ISO) by low and high doses of each drug. Beta-2 blockade was assessed using the attenuation of ISO-induced reductions in diastolic blood pressure (DBP) in Study 2 and ISO-induced increases in specific airway conductance (sGAW) in Study 3. For within drug comparisons, antagonism of the HR increase induced by ISO (a response mediated by both beta-1 and beta-2 receptors) was also examined. Treatments included cetamolol (15 and 60 mg), atenolol (50 and 200 mg), and nadolol (40 and 160 mg in Study 2; 40 mg only in Study 3). All drugs tested suppressed the HR, DBP, and sGAW responses to ISO, and this blockade was dose dependent. Cetamolol and nadolol produced approximately equipotent beta-1 blockade, whereas cetamolol at both doses produced a less potent beta-2 blockade. Atenolol antagonized ISO effects on all parameters less than either cetamolol or nadolol. Quantitative cardioselectivity indices revealed that cetamolol 60 mg was the most cardioselective and nadolol 40 mg the least. Data from the three studies demonstrate that cetamolol is cardioselective relative to nadolol and that, in contrast to atenolol, cardioselectivity appears to increase at the higher dose.

Acetamides↗

Function of the autonomic nervous system in young, untreated hypertensive patients.

The reactivity of the sympathetic nervous system was studied in 10 young, adult patients with labile hypertension and compared with a normotensive age-matched control group. Upon graded exercise on a constant speed bicycle ergometer, the hypertensive subjects reacted with an exaggerated blood pressure response and a significantly greater increase in the plasma adrenaline and noradrenaline levels. The basal catecholamine levels, however, were similar in both observation groups. This was in spite of an intact baroreceptor reflex in the hypertensives as indicated by a normal hemodynamic response to angiotensin II. This apparent discrepancy may be explained by an enhanced uptake of adrenaline during stress into the neuron, where it acts as a cotransmitter and facilitates the release of noradrenaline via presynaptic beta 2-adrenoceptors. Similar blood pressure and heart rate responses to isoproterenol and atropine were observed in both groups. This indicates normal beta-adrenoceptor sensitivity and vagal nerve activity in the hypertensive subjects.

Adult↗

A clinical approach for the identification of peripheral pre- and post-synaptic alpha-adrenergic receptors.

The present study examines the possibility that pre- and post-synaptic alpha-adrenergic receptors can be differentiated by a clinical pharmacological approach. We compared the ability of the alpha 1-selective antagonists, prazosin and urapidil, with the ability of the alpha 2-selective antagonist, yohimbine, to inhibit cardiovascular responses to the non-selective alpha-adrenergic agonist norepinephrine in 26 healthy volunteers. Urapidil (50 mg i.v.) and prazosin (5 mg orally) induced significant shifts to the right in the blood pressure dose-response curve of norepinephrine. Yohimbine (10 mg orally), on the other hand, increased norepinephrine sensitivity, as indicated by a significant shift to the left of the norepinephrine dose-response curve. In addition, urapidil and prazosin decreased norepinephrine potency on heart rate, whereas no effect on norepinephrine-induced heart rate elevation was observed with yohimbine. From the studies in which yohimbine was used it can be assumed that the post-synaptic response to norepinephrine is not counteracted by the drug-induced inhibition of sympathetic neurotransmitter release. Hence, our findings confirm the presence of pre- and post-synaptic alpha-adrenergic receptors in man.

Adult↗

[Vasodilator therapy in pulmonary hypertension and chronic obstructive lung disease (COPD). Hemodynamic studies exemplified by nifedipine and nitroglycerin].

In 41 patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension, the effects of sublingual administration of 20 mg nifedipine and 0.8 mg nitroglycerin on the hemodynamics were assessed at rest and during bicycle ergometry. Additionally, in six patients, the effects of nifedipine during longterm treatment were analyzed. On acute testing, at rest and during exercise nifedipine led to decreases in mean pulmonary artery pressure of 16% and 23% and pulmonary arteriolar resistance of 23 and 35%, respectively, in 81% (17/21) of the patients. The reduction in the pulmonary vascular resistance was greater than that of the systemic resistance. In all patients, cardiac output increased. There was a similar number of responders to nitroglycerin (16/20). The reductions in mean pulmonary artery pressure and pulmonary arteriolar resistance ranging between 20 and 25% at rest and during exercise were comparable to those affected by nifedipine. In addition to the right ventricular afterload reduction, there was a decrease in cardiac output of 17%. During longterm treatment with nifedipine (average 18 months), the reduction in mean pulmonary artery pressure and pulmonary arteriolar resistance was not of the same magnitude as seen on acute testing. This may be due primarily to progression of the underlying disease since pulmonary function studies demonstrated an increase in the obstructive component. With the intention of circumventing or postponing the onset of right ventricular failure, the individual patient should undergo hemodynamic studies to delineate the optimal medication.

Exercise Test↗

Post-heparin lipolytic activity in acute renal failure.

Total post-heparin lipolytic activity (PHLA), hepatic triglyceride lipase (HTGL) and protamine inactivated lipoprotein lipase (LPL) and plasma lipoprotein pattern were investigated in 8 patients with acute renal failure (ARF). PHLA was determined at 5, 10, 15, 30, 45 and 60 minutes after heparin administration (100 U/kg b.w.). Maximal PHLA in ARF was 6.12 +/- 1.56 mumol FFA/ml/h at 10 minutes versus 14.62 +/- 4.29 at 45 min in controls (= 42%, p less than 0.001). PHLA was reduced in ARF throughout the study period (p less than 0.001). Maximal HTGL activity (3.06 +/- 0.84 mumol FFA/ml/h) was obtained at 10 min in ARF versus 8.97 +/- 3.11 after 15 min in controls (= 34%, p less than 0.001). HTGL in ARF differed from controls at all points of determination (p less than 0.001). LPL maximum was 3.12 +/- 1.93 mumol FFA/ml/h at 15 min in ARF and 7.65 +/- 3.44 at 45 min in controls (= 40%, p less than 0.001). LPL activity was different from controls at 30, 45 and 60 min (p less than 0.001) but not at 5, 10 and 15 min after heparin injection. Due to a rapid decrease of LPL activity (half maximal activity after 34 min in ARF versus 94 min in controls, p less than 0.05) activity half life of PHLA was diminished in ARF (49 min in ARF versus 112 min in controls, p less than 0.01). Thus both the activity of HTGL and LPL is impaired in ARF. Because of the different activation kinetics of the two PHLA fractions no conclusions concerning maximal enzyme activities can be drawn from single determinations as suggested in previous studies on chronic renal failure.

Acute Kidney Injury↗

Diltiazem and verapamil: functional antagonism of exogenous noradrenaline and angiotensin II in man.

To evaluate the possible functional antagonism of the calcium antagonists diltiazem and verapamil of the sympathetic nervous system and the renin-angiotensin system, their influence on blood pressure, heart rate, plasma catecholamines and renin activity (PRA), and on the reaction of these parameters to exogenous noradrenaline (NA) and angiotensin II, was investigated in 8 normotensive volunteers. Intravenous diltiazem or verapamil caused a sharp, shortlasting decrease in systolic and diastolic blood pressure, with a maximum 1-3 min after injection and a duration of 10-15 min. Even a further infusion of the calcium antagonists was unable to maintain the initial hypotensive effect. The cessation of the hypotensive effect was not due to reflex stimulation of the sympathetic nervous system, as indicated by unchanged plasma NA and adrenaline levels in the case of diltiazem, but was associated with an increase in PRA. During the administration of diltiazem and verapamil, the increase in blood pressure in response to the infusion of NA and angiotensin II was attenuated; the increase in diastolic pressure was mainly affected. The inhibition was more pronounced at the higher infusion rate of NA and angiotensin II. On the basis of these findings it is suggest that the hypotensive activity of calcium antagonists can be at least partly attributed to a reduction in vascular tone which is maintained by the postjunctional action of noradrenaline and angiotensin II.

Adult↗

The diltiazem-digoxin interaction.

To study the interaction between the calcium antagonist diltiazem and digoxin, a randomized crossover trial under steady-state conditions was carried out in 24 healthy male subjects. Diltiazem with digoxin induced an average increase of steady-state plasma digoxin concentration and AUC over 48 hr of 22.4%. This is caused by the prolongation of elimination t1/2 from 36.2 +/- 11.2 to 44.5 +/- 11.5 hr (means +/- SD) and the impairment of total digoxin clearance, dropping from 146.6 +/- 37.9 to 107.9 +/- 18.4 ml/min. Average reduction in renal clearance (from 102.1 +/- 35.5 to 85.5 +/- 42.7 ml/min) was not statistically reproducible. Apparent volume of distribution was not relevantly altered. Diltiazem kinetics did not change significantly when digoxin was concurrently given.

Adult↗

[Therapeutic problems in hyperkinetic heart syndrome].

At present beta-blockers are the therapy recommended in hyperkinetic heart syndrome. This therapeutical advice was investigated by two cross over studies: the first trial was a comparison between the circulatory effects of Celiprolol and Pindolol, the second one between Oxprenolol and the calcium antagonist Verapamil. All beta-blockers tested effected a safe reduction in heart rate, which is elevated in hyperkinetic state, but failed to lower diastolic blood pressure by at least 15 mm Hg. Verapamil however, also effected bradycardia but did not reduce heart-rate in the same amount as beta-blockers. Furthermore the calcium antagonist's hypotensive effects are more pronounced by comparison with beta-blockers. According to these findings beta-blockers are not to be seen as therapy of first choice in hyperkinetic heart syndrome, they are only recommended combined with diuretics or vasodilators. As alternative therapy Verapamil could be prescribed, which disadvantage is the necessity of taking it several times per day.

Adrenergic beta-Antagonists↗

Indication of reduced doxorubicin-induced cardiac toxicity by additional treatment with antioxidative substances.

The influence of antioxidative substances on doxorubicin-induced cardiac toxicity was studied in C 57 BL mice. Tocopherol (500 mg/kg), glutathione (1000 mg/kg), cysteamine (15 mg/kg) and L-cysteine (1000 mg/kg), injected i.p. 24 h before doxorubicin treatment (15 mg/kg i.p.) were able to reduce malonaldehyde production in cardiac tissues significantly. SH-containing substances with high reducing activity, such as vitamin E, could be a useful tool in clinical trials to prevent doxorubicin induced cardiac damage.

Animals↗

Norfenefrine: haemodynamic effects in healthy volunteers at rest and during orthostasis.

The haemodynamic effects of the alpha-mimetic norfenefrine 1.5-4.5 micrograms/kg/min i.v. were studied by invasive methods in six healthy male volunteers at rest and during orthostasis (90 degrees on tilt table). Norfenefrine was more effective at rest and during exercise in raising blood pressure in the pulmonary than in the systemic arterial system. It was concluded that norfenefrine should be effective in the treatment of patients with orthostatic dysregulation due to reduced venous tone.

2-Hydroxyphenethylamine↗

Plasma concentration of cutaneously applied trinitroglycerin.

The absorption of trinitroglycerin ointment was studied on ten test persons over a 12-h period. The first plasma concentrations above the minimally detectable levels were found from the 10th min on. A first peak of absorption is measureable at 30 min. The inter- and intraindividual variations in the degree of absorption are most probably due to variability of absorption and various bioavailability. The absorption process can be substantiated during the entire time in which the ointment daub is in place. Typical trinitroglycerin effects such as reduction of blood pressure, elevation of heart rate, and increase in headaches were observed in healthy volunteers.

Administration, Topical↗