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Biomedical subjects

V B Fiedler

Publications and source records attributed to V B Fiedler.

At least 37 records · Page 2Linked to original sources
PubMed1985

Treatment of haemodynamic and electrocardiographic side-effects resulting from imipramine toxicity in rats and dogs.

This study was designed to analyze the effects of carbocromene and dipyridamole on the haemodynamic and electrocardiographic side-effects resulting from imipramine infusion in anaesthetised rats and dogs. Imipramine was infused at 1 mg/kg/min until cardiac failure and vascular collapse terminated the experiment at 21 +/- 2.3 min in rats and at 29.5 +/- 2.1 min in dogs. This was characterized by hypotension, bradycardia, intraventricular conduction delay, cardiac tachyarrhythmia and A-V block. Carbocromene (4 mg/kg i.v., followed by 80 micrograms/kg/min) protected the animals against heart failure. This was associated with delayed hypotension and negative inotropy, and lower incidence of heart block. Survival time increased to 37 +/- 1.5 min (P less than 0.05), and 54.2 +/- 2.6 min (P less than 0.02) in rats and dogs, respectively. Dipyridamole (0.5 mg/kg i.v., followed by 80 micrograms/kg/min) failed to decrease imipramine toxicity as judged by the haemodynamic and electrocardiographic parameters and did not alter survival time of imipramine controls. These results suggest that carbocromene is an effective treatment for imipramine-induced cardiovascular collapse and cardiac arrhythmias, the beneficial effects being largely due to metabolic and membrane stabilizing effects. Carbocromene has both therapeutic and prophylactic value and appears to be superior to dipyridamole therapy.

Animals↗
PubMed1985

Molsidomine on cardiovascular leukotriene D4 actions.

Anaesthetized open-chest dogs were used to study the effects of intracoronary leukotriene D4 (LTD4; 0.5 micrograms/kg) on haemodynamics, the electrocardiogram (ECG), coronary blood flow in the left circumflex artery and coronary resistance in the absence or presence of the antianginal drug molsidomine (500 micrograms/kg i.v.). LTD4 increased left ventricular (LV) filling pressure from 6.5 +/- 3.8 to 14.7 +/- 3.2 mm Hg (P less than 0.01), decreased LV dP/dtmax from 2,500 +/- 200 to 1,240 +/- 205 mm Hg/s (P less than 0.05), elevated the S-T segment of the ECG from 0.3 +/- 0.2 to 2.4 +/- 0.6 mV (P less than 0.01), and coronary resistance from 3.4 +/- 0.9 to 33.7 +/- 4.8 mm Hg X min X ml-1 (P less than 0.001). Coronary artery blood flow fell from 33.8 +/- 2.7 to 3 +/- 3 ml/min (P less than 0.001). Molsidomine treatment 15 min prior to repeated intracoronary LTD4 application attenuated vasoconstrictor response to LTD4 and the subsequent elevation in total coronary vascular resistance. The negative inotropic actions of the eicosanoid were counteracted by molsidomine. Filling pressure decreased and no temporary signs of ischaemia were noted in the ECG. Inhibition of the cyclooxygenase enzyme activity by i.v. indomethacin (5 mg/kg) had no effects on the LTD4-induced haemodynamic alterations, the ECG, and coronary flow and resistance. The antagonistic molsidomine actions on haemodynamic and electrocardiographic LTD4 effects were not influenced by previous indomethacin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1985

The effects of nafazatrom in an acute occlusion-reperfusion model of canine myocardial injury.

The effects of lipoxygenase enzyme inhibitor nafazatrom on infarct size, haemodynamics, and prostanoid release was studied in a canine occlusion-reperfusion model of ischaemic myocardial injury. Treatment was with 10 mg/kg nafazatrom i.d., starting before coronary occlusion, 2 h and 6 h thereafter, and was repeated in 6 h intervals. The left anterior descending (LAD) coronary artery was occluded for 6 h and reperfused for 42 h. Infarct size and anatomic area dependent on the occluded LAD were determined post mortem by the tetrazolium staining technique. Nafazatrom significantly reduced the extent of irreversible myocardial ischaemic damage whether it was expressed as g/100 g left ventricle (24 +/- 4 vs. 46 +/- 6 in controls; p less than 0.01; mean +/- SEM) or as percentage of LAD risk region for infarcting (38 +/- 8 vs. 65 +/- 7% in controls; p less than 0.05). Nafazatrom did not affect peripheral haemodynamics but during drug vehicle treatment and LAD occlusion systemic blood pressure, left ventricular pressure and dP/dtmax decreased while filling pressure, heart rate, and the S-T segments of the ECG increased. The incidence of ventricular fibrillation was 8% during drug treatment and coronary ligature vs. 25% in controls (n.s.). During reperfusion, nafazatrom reduced the incidence of ventricular premature contractions and tachycardia. Ex vivo platelet aggregation in response to collagen was not inhibited by nafazatrom. Prostanoid release (thromboxane B2 and 6-keto-prostaglandin F1 alpha as breakdown products of thromboxane A2 and prostacyclin, respectively) remained unaltered in vehicle controls but nafazatrom treatment elevated prostacyclin release significantly at 4 and 5 h during LAD occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Leukotrienes on porcine hemodynamics and prostanoid release.

We studied the effect of intracoronary leukotriene B4, C4, D4 and E4 (0.1-3 micrograms) on coronary artery blood flow and resistance in anesthetized pigs. Conventional hemodynamics were measured, and the peripheral electrocardiogram was obtained in lead II. Thromboxane B2 and 6-keto-prostaglandin F1 alpha (as breakdown products of thromboxane and prostacyclin, respectively) were measured during the influence of leukotrienes on the heart. All leukotrienes except B4 reduced coronary flow. Peak reduction was produced by 3 micrograms of each eicosanoid: C4 = 96 +/- 4%+; D4 = 98 +/- 2%+; E4 = 82 +/- 8%+. Coronary resistance increased after the same dose B4 = 65 +/- 18%; C4 = 225 +/- 94% (P less than 0.01); D4 = 442 +/- 118%+; E4 = 110 +/- 43% (+ = P less than 0.001). Increase in filling pressure and heart rate but blood pressure reduction and diminution in left ventricular d P/dtmax were observed with leukotriene C4, D4 and E4. The S-T segments of the electrocardiogram were elevated, thus indicating myocardial ischemia during the blood flow reduction. Indomethacin (5 mg/kg i.v.) had no effects on the leukotriene-induced hemodynamic sequelae. Thromboxane B2 concentration in coronary sinus blood plasma increased by 132-176% (P less than 0.05) at peak leukotriene effects on blood flow. Thus, leukotriene C4, D4, and E4 are vasoconstrictors in the situ porcine heart. Leukotriene B4, however, exerts no hemodynamic effects. The electrocardiographic ischemia and changes in hemodynamics indicate actions on coronary resistance and myocardial depression. These eicosanoids may contribute to cardiac dysfunction and vasospasm in coronary artery disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Influence of prostacyclin on coronary thrombosis and myocardial ischemia in conscious canine experiments.

The effects of intraventricular infusion of prostacyclin (PGI2; 50, 100 ng/kg/min) on hemodynamics, the ECG, coronary thrombosis and myocardial ischemia were studied in chronically equipped, resting conscious dogs and compared to those of intracardiac administration of Tris-HCl as vehicle. Coronary thrombosis was induced by electrical stimulation of an artery over an implanted wire for 6 hr. PGI2 infusion at 100 ng/kg/min decreased blood pressure by 24 +/- 3% (p less than 0.01) for 5 hr, increased heart rate at 1 hr by 28 +/- 4% (p less than 0.05) followed by a decrement, and elevated cardiac output by 41 +/- 3% (p less than 0.05). Filling pressure and dP/dtmax did not change. Treatment with PGI2 prevented ischemic S-T segment alterations in the ECG and arrhythmias observed in controls. The prostanoid infusion reduced coronary thrombus weight from 64 +/- 7.8 mg (mean +/- S.D.) in controls to 10.7 +/- 6.3 mg and 5.2 +/- 7.1 mg (both p less than 0.001) after 50 and 100 ng/kg/min, respectively. It also reduced myocardial ischemia following occlusive coronary thrombosis from 48 +/- 12% of the left ventricle in controls to 8.8 +/- 8.7% (p less than 0.01) and 2.4 +/- 5.2% (p less than 0.001) in the hearts treated with 50 or 100 ng/kg/min PGI2. The results suggest that PGI2 infusion exerts beneficial effects on heart performance by long-lasting blood pressure reduction and elevation of cardiac output caused by dilation of arterial vessels. PGI2 infusion prevents occlusive coronary artery thrombosis in response to intimal damage by anti-thrombotic properties and vasodilation of coronary arteries. This protects the heart from ischemia observed in controls.

Animals↗
PubMed1984

Nifedipine on cardiovascular leukotriene D4 actions in the anaesthetized dog.

Open-chest dogs were used to study the effects of intracoronary leukotriene (LTD4; 0.5 microgram/kg) on haemodynamics, coronary blood flow in the left circumflex artery and coronary resistance in the absence or presence of nifedipine (10 micrograms/kg, i.v.). LTD4 increased ventricular filling pressure by 133% (P less than 0.001), the S-T segments and coronary resistance by 490% (P less than 0.001) and abolished coronary flow for 3 min. Nifedipine pretreatment inhibited the cessation of coronary flow. No change in filling pressure and no ischemia signs in the peripheral ECG were noted. However, nifedipine did not inhibit the LTD4-induced decrease in left ventricular dP/dtmax. Haemodynamic LTD4 actions thus could be partially reversed by i.v. nifedipine, suggesting that leukotriene effects on the coronary and peripheral circulation are mediated by calcium release.

Anesthesia↗
PubMed1984

Leukotriene D4-induced vasoconstriction of coronary arteries in anaesthetized dogs.

We examined in pentobarbital-anaesthetized dogs, the effects of intracoronary leukotriene D4 (LTD4) on large vessel (circumflex artery) flow and diameter and on calculations of late diastolic and total coronary resistance. Heart rate, systolic and end-diastolic ventricular pressures and the dP/dt were the haemodynamic variables studied. The peripheral ECG was obtained in lead II. LTD4 (0.1-10 micrograms kg-1) reduced coronary diameter up to 12 +/- 3% (mean +/- s.e.m.). Coronary flow decreased in dose-dependent fashion up to 100%. Blood flow returned to control values within 3-15 min of LTD4 administration. Blood pressure, heart rate and ventricular pressure did not change while LV dP/dtmax fell and filling pressure increased. The sum of ST segments and R wave voltages of the ECG increased indicating transient myocardial ischaemia during LTD4-induced coronary blood flow cessation. Small vessel and total coronary resistance rose in a dose-dependent manner between 33-232% and 50-500%, respectively. Inhibition of cyclo-oxygenase enzyme (indomethacin, 5 mg kg-1, i.v.) and lipoxygenase enzymes (nafazatrom, 10 mg kg-1, i.d.) had no effect on LTD4-caused alterations in coronary flow, resistance and arterial diameter. Thus, in canine experiments the intracoronary administration of LTD4 can constrict coronary arteries--presumably large conductive vessels. This is independent of the cyclooxygenase and additional lipoxygenase metabolites of the arachidonic acid pathway other than LTD4. Therefore, the agent may contribute to cardiac dysfunction in coronary artery disease and spasm.

Animals↗
PubMed1984

Effects of dihydroergotamine on hemodynamic molsidomine actions in anesthetized dogs.

In pentobarbital-anesthetized mongrel dogs the intravenous actions of 0.50 mg/kg molsidomine on pulmonary artery and left ventricular (LV) end-diastolic pressures and internal heart dimensions (preload), left ventricular systolic and peripheral blood pressures, and total peripheral resistance (afterload), as well as on heart rate, dP/dt, stroke volume, and cardiac output (heart performance) were studied for 2 h. Hemodynamic molsidomine effects were influenced by increasing amounts of intravenously infused dihydroergotamine solution (DHE, 1-64 micrograms X kg-1 X min-1). Molsidomine decreased preload, stroke volume, and cardiac output for over 2 h but decreased ventricular and peripheral pressures for 45 min. Systemic vascular resistance showed a tendency to decrease while heart rate and LV dP/dtmax were not altered. DHE infusion reversed molsidomine effects on the preload and afterload of the heart. The diminished stroke volume was elevated so that cardiac output also increased. Total peripheral resistance increased while heart rate fell in a dose-dependent fashion. The LV dP/dtmax remained unchanged until the highest dose of 64 micrograms X kg-1 X min-1 DHE elevated the isovolumic myocardial contractility. These experiments indicate that DHE can reverse the intravenous molsidomine effects on hemodynamics. Most likely, this is mediated through peripheral vasoconstriction of venous capacitance vessels, thereby affecting molsidomine's action on postcapillary beds of the circulation.

Anesthesia↗
PubMed1983

Reduction of myocardial infarction and dysrhythmic activity by nafazatrom in the conscious rat.

The effects of nafazatrom (30 and 100 mg/kg b.i.d.) on myocardial lesions caused by coronary artery ligation were determined in rats. The treatment lasted ten days preceding and twenty days following the cardiac insult, and its effects were compared with the effects of oral 1% Tylose suspension as drug vehicle. Nafazatrom reduced the number of extrasystoles and the duration of ventricular tachycardia and fibrillation occurring in the early (0-10 min) and late phases (2-4 h) of cardiac arrhythmias observed in the controls. Pretreatment with nafazatrom reduced the size of the ultimate infarct by 36 and 48 percent (P less than 0.05), and by 28 and 39% (P less than 0.05) with post-ligature nafazatrom treatment.

Animals↗
PubMed1983

Analysis of oral molsidomine effects on ventricular function and dimensions in the conscious dog.

The effects of oral administration of molsidomine (50, 100 and 250 micrograms/kg) on left ventricular function, dimensions and hemodynamics were studied in chronically equipped, resting conscious dogs and compared to those of orally administered nitroglycerin (5, 10 and 20 micrograms/kg), as well as isosorbide dinitrate (50, 100 and 250 micrograms/kg). Enteral absorption of molsidomine was similar to that following intravenous administration of the compound, but was delayed in the case of both nitrates, so that restraint hemodynamic effects were noted. Molsidomine significantly decreased ventricular preload and internal heart dimensions. These effects were longer-lasting and more pronounced than those induced by either nitrate compound. Heart rate and LV dP/dtmax remained unaffected by molsidomine but increased in a dose-dependent fashion after administration of the nitrates. Left ventricular ejection phase contractility decreased with all three compounds. This effect was probably due to the reduced ventricular volumes and dimensions caused by molsidomine and isosorbide dinitrate, and to the additional tachycardia with concomitant reduction in ejection phase induced by nitroglycerin. Ejection time and stroke volume fell with all three agents but the effect occurred with a greater delay of onset and was more persistent after molsidomine. Nitroglycerin was found to increase cardiac output, initially, as a sequel of positive inotropy and chronotropy, with a subsequent decrease of cardiac output. In contrast, cardiac output fell by 28% and 30% (p less than 0.02) after administration of 250 micrograms/kg molsidomine or isosorbide dinitrate, respectively. These results suggest that molsidomine has no direct effects on myocardial hemodynamics and function in the resting, awake dog. The drug exerts its beneficial effects on heart performance by a long-lasting diminution of cardiac preload caused preferentially by dilatation of postcapillary venous vessels.

Administration, Oral↗
PubMed1983

Haemodynamic effects of pirlindole, a new tetracyclic antidepressant agent.

Cardiovascular dynamic, inotropic and electrophysiologic effects of the new tetracyclic antidepressant 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]-carbazole hydrochloride (pirlindole) (0.5, 1, 2.5, 5 and 10 mg/kg, i.v.) were investigated in anaesthetized dogs and compared with those of i.v. imipramine (0.5, 1, 2.5 and 5 mg/kg) administration. Noradrenaline (norepinephrine)-induced systemic blood pressure increase was significantly potentiated by imipramine but not by pirlindole. Severe hypotension was caused by most imipramine doses, whereas the initial blood pressure fall after pirlindole was followed by an increase. Heart rate did not alter with lower prilindole doses but increased after 2.5 mg/kg. Imipramine caused severe tachycardia. Pirlindole had no effects on contractility but imipramine was negative-inotropic. Left ventricular end-diastolic pressure fell after pirlindole; imipramine caused transient decrease in filling pressure between 0.5 and 2.5 mg/kg, whereas 5 mg/kg significantly elevated this variable. Myocardial oxygen consumption increased with 5 and 10 mg/kg pirlindole but was reduced by imipramine. Pirlindole did not induce changes in the electrophysiology of the heart. Imipramine decreased PQ-time and elevated ST-T segments indicating myocardial ischaemia. Imipramine effects on electrical conduction were deleterious so that no dog survived 10 mg/kg. These results suggest that pirlindole may be a possible therapeutic regimen for treatment of depressed human patients with a previous history of cardiovascular disease.

Animals↗
PubMed1982

The effects of molsidomine on intracranial pressure in anaesthetized dogs.

Measurements of intracranial liquor pressure were made during i.v. molsidomine administration in pentobarbital anaesthetized beagle dogs without thoracotomy, and compared with those after nitroglycerin. The administration of 100 micrograms/kg molsidomine decreased blood pressure by 14 mmHg and increased intracranial pressure by 3.7 cm H2O (P less than 0.05). No changes in heart rate and the alveolar end-tidal CO2 concentration were noted. The i.v. administration of 5 micrograms/kg nitroglycerin, however, decreased systolic blood pressure by 41 mmHg (p less than 0.05), increased heart rate by 40 bpm (p less than 0.01), elevated intracranial pressure by 3.2 cm H2O (p less than 0.05), and caused marked hyperventilation indicated by increased end-tidal CO2 concentration. Larger increases in intracranial pressure were related to larger pressure reductions. Thus, molsidomine produced significant increase in intracranial liquor pressure of longer duration (60 to 90 min of observation time). Nitroglycerin increased liquor pressure with a short duration of action and was about twenty time more effective with respect to intracranial pressure increase. In contrast to molsidomine, this was accompanied by significant decrease in systolic peripheral blood pressure.

Anesthesia↗
PubMed1982

Reduction of occlusive coronary artery thrombosis and myocardial ischemia by molsidomine in anesthetized dogs.

The antianginal drug molsidomine was evaluated for its in vivo antithrombotic effects in barbiturate-anesthetized open-chest dogs by inducing left circumflex (LCX) coronary artery thrombosis with low-amperage stimulation (150 microA for 6 h) of the intimal surface of the vessel. Intravenous bolus administration of 0.10 mg/kg molsidomine 10 min prior to onset of electrical stimulation partially prevented occlusive LCX thrombosis and prolonged time to complete vessel occlusion by 45 min (p less than 0.05). Intracoronary thrombus mass was reduced (14 +/- 0.8 vs. 32 +/- 4 mg in controls, p less than 0.05). Final 6-h infarcts after complete LCX coronary artery thrombosis were measured by triphenyltetrazolium chloride (TTC) staining and were smaller after molsidomine pretreatment when related to left ventricular mass (14 +/- 3 vs. 28 +/- 2%, p less than 0.02) or to the LCX vessel area at risk for infarction (18 +/- 3 vs. 58 +/- 4%, p less than 0.01). Molsidomine did not induce hemodynamic alterations during time to complete thrombotic LCX coronary artery occlusion. In saline controls, heart rate and end-diastolic pressure increased whereas blood pressure and contractility decreased significantly. The percentage of ventricular ectopic beats concomitant to thrombus formation and myocardial ischemia was significantly reduced in the drug-treated dogs. Molsidomine also partially prevented the reduction in myocardial function parallel to blood flow diminution as measured with an ultrasonic technique. The drug further exerted significant ex vivo inhibition of collagen-induced platelet aggregation (p less than 0.01 vs. control from 4 h after onset of LCX stimulation). In addition to established hemodynamic effects of molsidomine there may also be a direct effect on platelet aggregation and thrombus formation in vivo which delays coronary artery narrowing and occlusion as one primary cause for myocardial ischemia.

Animals↗
PubMed1982

Effects of carbocromene on ventricular fibrillation during acute myocardial ischemia in anesthetized dogs.

The effects of carbocromene, 4 mg/kg intravenously, prior to coronary artery occlusion plus 40 microgram/kg/min during coronary artery occlusion and reperfusion on ventricular fibrillation threshold (VFT) were studied in pentobarbital-anesthetized open-chest dogs and compared to controls receiving saline. Coronary artery occlusion decreased VFT by 46 +/- 4% (mean +/- SEM, p less than 0.02) in controls and by 22+/-3% in drug-treated animals. Reperfusion of the occluded artery decreased VFT by 83+/-7% (p less than 0.01) in controls and by 47+/-5% in carbocromene-treated hearts (p less than 0.02). Hemodynamics did not change in the drug group during coronary artery occlusion. In controls, blood pressure and dP/dtmax decreased while heart rate, end-diastolic pressure and ST-T segments increased significantly during both coronary artery occlusion and reperfusion. The underperfused, ischemic region was assessed by staining with Evans blue and involved 34+/-3% of the left ventricular mass in controls but only 27+/-3% in carbocromene-treated hearts (p less than 0.05). These results indicate protective effects of carbocromene on ventricular vulnerability in canine hearts during coronary artery occlusion and subsequent reperfusion.

Anesthesia↗
PubMed1982

Diagnostic exercise.

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Adrenal Gland Neoplasms↗
PubMed1981

Effects of molsidomine on coronary artery thrombosis and myocardial ischemia in acute canine experiments.

Antithrombotic and hemodynamic properties of molsidomine (0.10 mg/kg i.v.) were evaluated in an in-vivo model of coronary artery thrombosis initiated by electrical stimulation for 6 h. Molsidomine prolonged time to vessel occlusion and prevented heart rate and end-diastolic pressure increase and contractility decrease. Infarct size was smaller after drug treatment related either to left ventricle (P less than 0.02) or to vessel area-at-risk (P less than 0.01). It is suggested that molsidomine has antithrombotic effects which might prevent acute coronary infarction.

Animals↗