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S Gasic

Publications and source records attributed to S Gasic.

At least 73 records · Page 4Linked to original sources
PubMed1987

[Hepatic vein catheter technic: method for the detection of metabolic and hormonal variables in the splanchnic area].

The hepatic venous catheterization method permits calculation of net splanchnic output and uptake of substrates and hormones from their respective differences in hepatic venous and arterial concentrations as well as the rate of hepatic plasma or blood flow. Estimates of the latter are made possible by the continuous infusion technique using indocyanine green dye. With determination of splanchnic balance data at hand transsplanchnic and in part even transphepatic handling of metabolic substrates and hormones can be calculated.

Catheters, Indwelling↗
PubMed1987

Diltiazem counteracts digitalis-dependent splanchnic vasoconstriction in man.

We investigated the vasodilating effect of diltiazem on basal as well as digoxin-dependent splanchnic and systemic hemodynamics in 12 normotensive men, using the hepatic venous catheter technique, the thermodilution method and systolic time intervals. After baseline measurements, diltiazem was administered by a primed-constant infusion (2.5 micrograms/kg/min) in 6 out of 12 subjects. Following an equilibration period of diltiazem infusion, 1 mg digoxin was infused concomitantly over 15 min and hemodynamic changes were determined over 105 min. Control trials with digoxin and concomitant saline infusion were also performed in 7 out of 12 subjects. Diltiazem medication alone lowered only systolic blood pressure without affecting splanchnic hemodynamics. Digoxin without comedication provoked an increase in systolic blood pressure, a decrease in heart rate, mean pulmonary artery pressure and total electromechanical systole (positive inotropic effect), and significantly reduced splanchnic blood flow and increased splanchnic vascular resistance. During concomitant diltiazem infusion, digoxin did not alter splanchnic hemodynamics while the shortening of total electromechanical systole remained unchanged. We conclude, that diltiazem attenuates digoxin-induced splanchnic vasoconstriction and therefore, might be useful in the treatment of digitalis-dependent splanchnic vascular insufficiency.

Adult↗
PubMed1987

Comparative effects of verapamil, tiapamil, diltiazem and nifedipine on systemic and splanchnic hemodynamics in man.

The vasodilating effects of verapamil, tiapamil, diltiazem and nifedipine on splanchnic and systemic circulation have been investigated in 18 male normotensive subjects by means of the hepatic venous catheter technique, the thermodilution method and systolic time intervals. After a baseline period, calcium antagonists were administered by a primed-constant infusion. Hemodynamic changes were assessed after an adequate equilibration period. Verapamil did not change splanchnic or systemic hemodynamics. Tiapamil decreased diastolic blood pressure and systemic vascular resistance as well as splanchnic vascular resistance, and increased cardiac output. Diltiazem lowered only systolic blood pressure without effecting splanchnic circulation. The most pronounced vasodilating effect was seen with nifedipine. It significantly reduced systolic and diastolic blood pressure, systemic vascular resistance and also splanchnic vascular resistance. Our present data seem to indicate that nifedipine and tiapamil are more effective vasodilators, especially in the splanchnic vascular bed, as compared to verapamil and diltiazem. We conclude that these two calcium antagonists might be useful in the treatment of intestinal (splanchnic) vasoconstriction.

Adult↗
PubMed1986

Comparative pharmacokinetics and cardiovascular effects of tiapamil in healthy volunteers and patients with hepatic cirrhosis.

Tiapamil 70 mg was administered i.v. to 8 healthy male volunteers and 8 patients (7 males, 1 female) with biopsy proven hepatic cirrhosis. Two of the patients also received 600 mg p.o. Serial plasma and urine samples were collected and the parent drug in plasma and urine and desmethyl-tiapamil in urine were assayed by a specific HPLC method. The plasma and urine data for the parent drug after i.v. and p.o. dosing were simultaneously fitted to linear p.o. and i.v. two compartment models with exit from and input into the central compartment. Absorption was assumed to be a first order process. In the volunteers the mean pharmacokinetic parameters were: 101 l for the steady-state volume of distribution 750 ml X min-1 for nonrenal clearance, 195 ml X min-1 for renal clearance and 1.7 h for the half-life of the terminal disposition phase. The urinary recoveries of the parent drug and desmethyltiapamil averaged 21.4 and 0.8% of the dose, respectively. In the patients the steady-state volume of distribution, the amount of unchanged drug in urine and the half-life of the terminal disposition phase were significantly increased (171 l, 29.0% of the dose, 3.5 h, respectively). Decreased plasma protein binding in the patients accounted for the larger steady-state volume of distribution. The nonrenal clearance of 519 ml X min-1, tended to be smaller in the patients than in the volunteers. Together with the increased urinary recovery of tiapamil in the patients this indicates a moderately impaired elimination capacity in the cirrhotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Moclobemide, a new reversible MAO inhibitor--interaction with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients.

Moclobemide is a new, short-acting, reversible MAOI, preferentially affecting type A MAO. We have studied the interaction of moclobemide with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients. Neither tyramine capsules (50 mg) nor cheese and wine meals (65 mg tyramine) produced a significant change in blood pressure and heart rate after single or repeated doses of moclobemide in volunteers. In contrast, after 1 weeks' treatment with tranylcypromine pressure response to cheese and wine meals was severe. Blood pressure sensitivity to IV tyramine was slightly increased (1.5-2 fold; P less than 0.05 versus predrug) during moclobemide treatment in patients and volunteers. This increase was neutralised by concomitant administration of desipramine in volunteers. Amitriptyline was well tolerated when given to patients after or together with moclobemide. In conclusion, moclobemide appears relatively safe with respect to tyramine sensitivity and interaction with tricyclics.

Adult↗
PubMed1986

In vivo clearance of antibody-sensitized human drug carrier erythrocytes.

Antibody coating of resealed drug carrier erythrocytes may be useful for drug targeting to the reticuloendothelial system. We have investigated the survival in the circulation of anti-Rh antibody (IgG anti-D)-coated autologous erythrocytes loaded with gentamicin by hypoosmotic dialysis. Five subjects were injected with 15.2 +/- 0.4 ml and five additional subjects with 62.8 +/- 1.5 ml carrier cells. Survival of the cells was monitored by intraerythrocytic gentamicin concentration in blood. In the first subject group initial t1/2 was 0.21 +/- 0.06 hours and terminal t1/2 was 1.71 +/- 0.36 hours. In the second group initial t1/2 was 0.59 +/- 0.21 hours followed by a slow phase with a t1/2 of 89 +/- 28 hours. Results indicate that rapid drug delivery to the reticuloendothelial system by antibody-sensitized carrier erythrocytes is possible, but small volumes of erythrocytes seem more efficient.

Adult↗
PubMed1986

A drug interaction study of ceftriaxone and frusemide in healthy volunteers.

Ceftriaxone, a recently developed cephalosporin significantly reduced the diuretic activity of frusemide in rats. For this reason and because an interaction of unknown mechanism is well established between frusemide and some cephalosporins, we studied the interference of ceftriaxone with the diuretic effect of frusemide in healthy volunteers. Twelve subjects received frusemide (40 mg p.o.) or placebo in combination with ceftriaxone (2 g i.v.) or saline on 4 different days (cross-over, randomized, single-blind study). Urine was collected in small portions during 24 hours after medication and analyzed for volume, osmolality, Na+, K+, Cl- and creatinine concentration. Ceftriaxone had neither an effect on basal urinary output and electrolyte excretion nor on the specific diuretic action of frusemide.

Adult↗
PubMed1985

Release of vitamin B12 from carrier erythrocytes in vitro.

Resealed erythrocyte ghosts (carrier erythrocytes) are potential in vivo carriers for exogenous enzymes or drugs, but data on carrier erythrocyte survival and clearance rate in humans are not available. We have measured the in vitro efflux of vitamin B12 encapsulated in human red cell by hypo-osmotic dialysis, as a preliminary for its use as a marker for in vivo human studies. Vitamin B12 was encapsulated into erythrocytes at a relative incorporation efficiency of 60%. In vitro hemolysis of carrier erythrocytes was minimal over 40 h, but vitamin B12 was rapidly lost from the cells, efflux t/2 was 5 h, presumably by diffusion through the intact cell membrane. Vitamin B12 (Vit B12) may, nevertheless, be a suitable marker for short-term human studies on carrier erythrocyte splanchnic clearance.

Blood Specimen Collection↗
PubMed1985

Biochemical, physical and psychological findings in patients suffering from cardiac neurosis.

In 10 patients suffering from cardiac neurosis changes in plasma norepinephrine (NE) and epinephrine (E) were studied by an upright bicycle exercise and during psychological stress. Psychometric tests were also performed. 6 healthy subjects served as a control group. At exercise, no relevant differences in blood pressure and heart rate regulation between patients and controls were present. The NE and E increase was normal and similar in both groups. During psychological stress an equal plasma NE increase was seen in both groups. During recovery, however, a sustained release of NE was present in patients. It is concluded that patients with cardiac neurosis respond to psychological stress by an inappropriate sustained activation of the sympathetic nervous system.

Adult↗
PubMed1984

The effect of a new specific alpha-amylase inhibitor on post-prandial glucose and insulin excursions in normal subjects and Type 2 (non-insulin-dependent) diabetic patients.

Trestatin (Ro 9-0154), a new specific alpha-amylase inhibitor of microbial origin, was tested in six normal subjects and seven Type 2 (non-insulin-dependent) diabetic patients. In normal subjects the maximal increases in blood glucose following a 115-g starch meal were 2.19 +/- 0.57 mmol/l (mean +/- SEM) with placebo, but 1.32 +/- 0.39 mmol/l with 10 mg, 1.06 +/- 0.26 mmol/l with 20 mg, 0.43 +/- 0.07 mmol/l with 50 mg (p less than 0.05) and 0.26 +/- 0.14 mmol/l with 100 mg (p less than 0.05) Trestatin . The corresponding increases in plasma insulin were 116.5 +/- 19.6 mU/l; 74.8 +/- 17.5 mU/l; 50.7 +/- 8.3 mU/l; 28.7 +/- 6.9 mU/l (p less than 0.05) and 16.5 +/- 3.2 mU/l (p less than 0.05). In the diabetic patients the maximal increases in blood glucose following a 50-g starch meal were 6.09 +/- 0.02 mmol/l with placebo, but 3.17 +/- 0.59 mmol/l (p less than 0.05) with 10 mg and 1.69 +/- 0.41 mmol/l (p less than 0.05) with 30 mg Trestatin . The corresponding insulin increases were: 58.8 +/- 12.7 mU/l, 31.5 +/- 9.7 mU/l (p less than 0.05) and 23.4 +/- 4.8 mU/l (p less than 0.05). Trestatin fully retained this pharmacological activity during treatment for 4 weeks in the diabetic patients. Trestatin did not influence glucose and insulin profiles after oral glucose and sucrose. These results are consistent with a specific inhibition of alpha-amylase in man.

Adult↗
PubMed1984

Effect of cianopramine, a tricyclic antidepressant, on platelet serotonin uptake and peripheral adrenergic function.

Cianopramine, a new tricyclic antidepressant, is a potent inhibitor of neuronal serotonin (5-HT) uptake in animals. We studied the effect of cianopramine on 5-HT uptake (ex vivo) in platelets and on peripheral neuronal adrenergic function in catecholamine pressure response tests in normal subjects. The inhibition of 14C-labeled 5-HT uptake into platelets was 57% +/- 12% 2 hr after 0.5 mg (after 24 hr: 27% +/- 13%), 59% +/- 10% 2 hr after 1 mg (24 hr: 41% +/- 13%), and 80% +/- 2% 2 hr after 2 mg cianopramine (24 hr: 52% +/- 10%). Systolic blood pressure response to intravenous tyramine and norepinephrine was unchanged after 2 mg cianopramine. The phenylephrine dose required for an increase of 40 mm Hg in systolic blood pressure was 67 +/- 25 micrograms/min before cianopramine and 86 +/- 32 micrograms/min 2 hr after 2 mg cianopramine, which suggests weak alpha-receptor antagonism of cianopramine. Our results in man are consistent with potent, specific 5-HT uptake inhibition by cianopramine without a clinically relevant effect on peripheral neuronal norepinephrine reuptake.

Administration, Oral↗
PubMed1983

[Pharmacokinetics and acute signs of cardiac toxicity during doxorubicin therapy].

Doxorubicin (Adriamycin) has shown impressive activity in the treatment of a broad spectrum of malignant tumours. Chronic irreversible cardiac myopathy is the usual cumulative dose-limiting toxicity with this anthracycline antibiotic. In this study acute cardiac reactions following doxorubicin infusions (60 mg/m2) were registered by means of ECG Holter monitoring and measurement of systolic time intervals. The PEPI as well as the PEP/LVET ratio were found to be significantly increased, with a peak at 6 hours following drug infusion (p less than 0.001). This observation proves the occurrence of transient myocardial dysfunction during doxorubicin treatment. Pharmacokinetic data showed good correlation between the electrocardiographic changes and the tissue distribution of the drug. Doxorubicin-related ventricular arrhythmias were observed in only 2 out of 6 cases. Repeated acute myocardial damage by doxorubicin infusions is considered to be the cause of chronic cardiomyopathy with long-term administration.

Adult↗
PubMed1983

Cardiocirculatory effects of moclobemide (Ro 11-1163), a new reversible, a short-acting MAO-inhibitor with preferential type A inhibition, in healthy volunteers and depressive patients.

The benzamide-derivative moclobemide (Ro 11-1163) is a new short-acting, reversible MAO-inhibitor, preferentially affecting Type A MAO, which is, being developed as an antidepressant agent. The effect of moclobemide on heart rate, blood pressure, electrocardiographic and systolic time intervals was assessed in eight healthy volunteers and seven depressive patients. The volunteers received single doses of 100 mg, 150 mg and placebo in radomized single-blind order. Seven patients received placebo and 100 mg as single doses and five patients were also given chronic treatment with individually assessed optimal therapeutic dose (100-400 mg). No change in blood pressure, heart rate, ECG or systolic time intervals was found. The compound was well tolerated. The findings suggest that moclobemide may be a safe MAO-inhibitor as far as sympathetic responsiveness and cardiovascular effects are concerned.

Adult↗
PubMed1982

Cardiocirculatory effects of Ro 11-2465, a selective 5-HT (serotonin) uptake inhibitor, in healthy volunteers.

The imipramine derivative Ro 11-2465, a potent, selective 5-HT (serotonin) uptake inhibitor, is being developed as an antidepressant agent. The effects of Ro 11-2465 on heart rate, blood pressure, electrocardiogram and systolic time intervals were assessed in nine normotensive volunteers. Ro 11-2465 1 and 2 mg and a placebo were given in a single blind, cross over design study. The placebo did not induce any significant changes. With Ro 11-2465, the ECG-intervals (P, PQ, QRS, QTc) did not change, the blood pressure increased 3-6 h after administration of either dose, and the heart rate was increased 4-6 h after the 2 mg dose. There was also evidence of increased ventricular automaticity in one subject. the total electromechanical systole (QS2-index) was significantly shortened 4-8 h after administration of 2 mg, whereas neither 1 mg the dose nor the placebo had any such effect. This finding suggests the presence of a positive inotropic effect, which is probably due to a stimulatory effect of serotonin, and is not mediated by an adrenergic mechanism. The findings suggest that Ro 11-2465, as a potential new tricyclic antidepressant, might have favourable cardiocirulatory dose effects, particularly in patients with pre-existing heart disease.

Adult↗
PubMed1982

Acute antianginal effect of tiapamil.

In open and double-blind trials, tiapamil was given intravenously and/or orally to 22 patients with coronary heart disease and exertional angina. Multistage bicycle exercise tests were performed before and after drug treatment and patients acted as their own controls. Thallium-201 exercise myocardial imaging was also performed. Exercise tolerance increased and angina was improved under tiapamil treatment. Heart rate and blood pressure decreased slightly, consistent with reduced myocardial oxygen demand. Myocardial oxygen consumption, as indicated by the pressure-rate product, varied little, but exercise myocardial imaging indicated an increase in regional perfusion. The findings suggest that tiapamil is an effective antianginal agent.

Adult↗
PubMed1980

[The effect of the calciumantagonist dimeditiapramine on thallium-201 myocardial perfusion during exercise in patients with coronary heart disease (author's transl)].

The effect of dimeditiapramine (Ro 11-1781), a new calciumantagonist, on thallium-201 myocardial perfusion during exercise was studied in a double-blind trial with 10 patients suffering from coronary heart disease. Treatment with a single intravenous dose of 1 mg/kg body weight resulted in a significant regional thallium-201 perfusion increase in 8 out of 10 patients. These results correspond with the clinically observed decrease in exercise-induced angina and ischaemic ECG alterations. The findings indicate that dimeditiapramine might be a useful anti-anginal drug.

Aged↗
PubMed1979

Insulin production rate following glucose ingestion estimated by splanchnic C-peptide output in normal man.

Insulin production rate has been estimated in healthy male volunteers (n = 16), and evaluated with respect to splanchnic glucose exchange. Insulin production rate was calculated from splanchnic immunoreactive C-peptide output. C-peptide secretion was estimated by the hepatic venous catheter technique both in the basal state and for 2 h following ingestion of various glucose loads (0, 12.5, 25, 50, 75, and 100 g). The results demonstrate a basal insulin production rate of 0.017 +/- 0.002 U/min (mean +/- SEM) or 2.04 U/2 h. Values rose in a dose dependent manner from 2.6 +/- 1.1 U/2 h after ingestion of 12.5 g of glucose to 10.8 +/- 1.1 U/2 h following a glucose load of 100 g. Insulin retention by the liver was estimated at 0.012 +/- 0.001 U/min in the basal state, and ranged from 47-85% (70 +/- 2%) of production following an oral glucose load. It was also demonstrated 1) that the relative splanchnic glucose output was inversely related to the amount of ingested glucose, and reached a minimum when glucose in excess of 50 g was ingested; and 2) that hepatic glucose retention was directly proportional to insulin production rate (r = 0.83; p less than 0.001; n = 15). It is suggested that the adaptive capacity of the splanchnic bed to retain glucose depending on the amount of ingested glucose guarantees that splanchnic glucose output fluctuates in healthy man only within a narrow range.

Adult↗