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Biomedical subjects

V B Fiedler

Publications and source records attributed to V B Fiedler.

At least 55 records · Page 3Linked to original sources
PubMed1981

Effects of pulsatile and non-pulsatile perfusion on the isolated canine heart.

Isolated canine hearts with a critical stenosis on one coronary artery were perfused for 2 h with blood from supporting dogs using a new roller pump system that can deliver pulsatile or non-pulsatile flow perfusion. Non-pulsatile perfusion caused a decrease in coronary venous oxygen tension of 22% (P less than 0.05) accompanied by increasing carbon dioxide tension of 50% (P less than 0.02). With pulsatile flow coronary venous oxygen and carbon dioxide tensions remained stable. Non-pulsatile perfusion decreased the coronary arteriovenous oxygen difference by 35% (P less than 0.02), coronary blood flow by 40% (P less than 0.02), and myocardial oxygen consumption by 54% (P less than 0.01) whereas pulsatile flow did not change any of these variables. Subendocardial blood flow distal to the stenosis fell by 0.15 +/- 0.04 ml/min per gram myocardium (mean +/- S.E.M.) (P less than 0.01) during linear perfusion. The endocardial/epicardial-flow ratio was less than one and decreased further during fibrillation period indicating underperfusion of the endocardial muscle region. With pulsatile flow subendocardial flow remained unaltered during the two hours of fibrillation. Edema formation was 24% in hearts subjected to non-pulsatile flow but only 14% in hearts perfused by pulsatile perfusion (P less than 0.05). Accordingly, the ischemic area involved 40% of the left ventricle during non-pulsatile flow but 25% of the left ventricle in hearts perfused by pulsatile perfusion (P less than 0.05). The results indicate that pulsatile flow perfusion may prevent severe hemodynamic, hematologic, and metabolic alterations in fibrillating isolated canine hearts. It is suggested that pulsatile perfusion may be useful for fibrillating hearts during open heart surgery.

Animals↗
PubMed1981

Effects of carbocromene on myocardial oxygen consumption in isolated dog hearts.

In isolated empty beating and isovolumetrically working supported dog hearts, the effects of intracoronary administration of the antianginal agent carbocromene (chromonar) and its corresponding acid metabolite on coronary blood flow and myocardial oxygen consumption were investigated. After administration of 1.0 and 2.0 mg of carbocromene per heart, coronary flow increased significantly between 61 (P less than .05) and 155% (P less than .01) in both types of experiments. However, the carbocromene acid did not alter coronary flow. Both compounds decreased with the used doses myocardial oxygen consumption between 18 (P less than .05) and 36% (P less than .05) in empty beating as well as in working hearts. Both agents did not cause significant changes in heart rate and inotropy of the isolated hearts in both types of experiments. It is suggested that carbocromene decreases myocardial oxygen consumption by a direct effect on myocardial oxygen metabolism as is evident from the fact that this decrease is not accompanied by changes in any of the parameters which influence oxygen consumption. This effect of the drug is independent from its coronary vasodilating properties as the metabolite doses not change coronary flow but decreases myocardial oxygen consumption in both types of experiments.

Animals↗
PubMed1981

Effects of 1-(5'-oxohexyl)-3-methyl-7-propylxanthine (HWA 285) on viability of ischemic jeopardized myocardium after acute coronary artery occlusion and reperfusion.

The effects of the xanthine derivative 1-(5'-oxohexyl)-3-methyl-7-propylxanthine (HWA 285) (0.5 mg/kg plus 50 micrograms/kg/min i.v.) on hemodynamics, electrical activity, infarct size, hemorrhage and survival after 90 min occlusion and 30 min reperfusion of one coronary artery were investigated in anesthetized, open-chest dogs in acute experiments. After transient, short-lasting effects prior to coronary artery occlusion the compound did not significantly alter systemic blood pressure, left ventricular pressure, contractility, and the tension-time-index as a measure for myocardial oxygen consumption during coronary artery occlusion and subsequent reperfusion. However, heart rate, left ventricular end-diastolic pressure, and the sum of ST-segment elevation were significantly increased particularly after onset of reperfusion, but the agent prevented severe arrhythmias during vessel occlusion and reperfusion. Infarct size and the amount of hemorrhage after flow release both were significantly smaller in the HWA 285-treated hearts than in saline-treated control hearts (p less than 0.05 in both cases), and the survival rate was higher in the compound group than in the saline controls. These data suggest a cardioprotective effect of HWA 285 in acute canine experiments undergoing coronary artery occlusion and reperfusion, probably due to antiarrhythmic and/or metabolic properties of the compound.

Animals↗
PubMed1980

Determination of left ventricular dimensions with ultrasound.

A new ultrasonic measuring system (UM 3) is described. In addition, the construction of simple piezoelectric transducers is outlined. These can be implanted either in the epicardium or in the endocardium of the left ventricle in anesthetized or conscious dogs. The total system has a high accuracy and linearity, and zero drift is small. An automatically controlled floating window excludes most artifacts due to unwanted echoes. Together with a modified delay-time measuring circuit, better recordings of dimensions are obtained. Sources of error due to the technique of implantation or due to electrical disturbances are described. A modified technique of implantation of endocardial transducers is presented.

Animals↗
PubMed1980

[The effects of oral carbocromen on the therapeutic and toxic effects of digitalis].

The arrhythmogenic and lethal doses of digoxin i.v. were determined in anaesthetized dogs, pretreated orally with placebo or with carbocromen 3-(2-diethylaminoethyl)-4-methyl-7-carbethoxy-methoxy)-2-oxo-1,2-chromene-hydrochloride (carbocromen, Intensain retard). Measurements of heart rate and dpldtmax during constant infusion of digoxin should demonstrate possible interference of carbocromen with the therapeutic effects of digoxin. Pretreatment of the animals (3--5 weeks) with carbocromen leads to strong protection against toxic effects of digoxin even 16--20 h after last dosing. Single oral application 1 h prior to anaesthesia also has a strong protective action. The behaviour of heart rate and dpldtmax in the treated animals is not different from that in the placebo group. The design of experiments and the results allow the conclusion that the different pharmacokinetics of carbocromen (serum) as compared to digoxin is of no consequence because the protective effects are not correlated to plasma levels.

Animals↗
PubMed1980

Effects of intravenous carbocromene on infarct size following acute coronary artery occlusion and reperfusion in the dog.

The effects of the antianginal drug carbocromene on hemodynamics, infarct size, and arrhythmias after 90 min of coronary artery occlusion and following 30 min reperfusion were investigated in anesthetized, open-chest dogs. Carbocromene led to only slight pressure and rate alterations after ligation and reperfusion whereas untreated animals gave evidence of significant changes in these parameters. Furthermore, contractility remained unaffected by carbocromene but was significantly augmented in the control group after both experimental procedures. Preload (end-diastolic pressure) increased after occlusion and reperfusion in both groups, and this augmentation was permanently higher in the controls than in the carbocromene group. Increases in oxygen consumption and in ST-segment elevation were small after drug treatment but significant in control animals. Infarcted areas were significantly smaller in the carbocromene group than in the controls. Hemorrhage occurred in both groups but the amount was significantly smaller in the drug group. The onset of arrhythmias was delayed in the carbocromene group after ligation and reperfusion so that the mortality was significantly lower as compared to that in the non-treated control animals. Carbocromene possibly exerts metabolic effects on the heart, in addition to its coronary dilating properties, which confer the cardioprotective effects observed in acute canine experiments.

Animals↗
PubMed1978

[Effects of molsidomine and nitroglycerin on the regional blood flow in the normal and acutely ischemic myocardium (author's transl)].

In anaesthetized dogs regional myocardial blood flow (radioactive particle distribution technique) and several haemodynamic parameters were measured before and after acute ligation of left descending coronary artery. By injection of N-carboxy-3-morpholino-sydnonimine ethylester (molsidomine, Corvaton) or infusion of nitroglycerin it was tried to influence blood flow of the infarcted areas of the myocardium. 1. Ligation of the coronary artery induces myocardial infarction of anterior wall, predominantly restricted to the endocardial portions of the heart muscle. 2. Molsidomine and also nitroglycerin do not change overall blood flow of the heart in the sense of vasodilation. 3. In the infarcted area the ratio: blood flow of endocardial layers to blood flow of epicardial layers, is improved by molsidomine. 4. The positive effect of molsidomine becomes clearer in the border zone of infarction. Nitroglycerin remains without effect. 5. The effects of the compound molsidomine are explained by stronger action on extravascular factors of colonary vascular resistance (decrease in enddiastolic pressure).

Animals↗
PubMed1978

Haemodynamic effects of molsidomine.

The haemodynamic effects of N-carboxy-3-morpholino-sydronimine-ethylester (molsidomine, SIN 10, Corvaton) were studied in anaesthetized mongrel dogs. The effects of molsidomine were identical when given i.v. or i.d. Because of the lack of difference in activity with similar doses i.v. or i.d. complete absorption of the drug can be assumed. There was a sustained decrease in arterial blood pressure accompanied by a long lasting decrease in left ventricular enddiastolic and mean pulmonary artery blood pressure. Heart rate was only moderately affected. Left ventricular endsystolic and enddiastolic volumes, as estimated from measurements of left ventricular outer dimension with ultrasonic techniques, decreased. Even in nearly toxic doses molsidomine did not influence left ventricular contractility as judge from measurements of dp/dt max., (dp/dt)/(LVP-LVEDP + c) max., ejection time and duration of systole. All the observed effects of molsidomine can be explained by an extracardiac action: increase in systemic venous capacity. Consequently venous return, mean pulmonary artery pressure and left ventricular filling pressure are reduced leading to a decrease in left ventricular volumes. This should cause a reduction of cardiac output, of peripheral blood pressure and of external cardiac work. In connection with reduced left ventricular wall tension a fall in myocardial oxygen consumption can be expected.

Animals↗
PubMed1978

[Effect of molsidomine on the regional distribution of cardiac output in the anaesthetized dog (author's transl)].

In anaesthetized dogs blood pressures were measured in the following parts of the circulation: A. femoralis, aorta, left ventricle and A. pulmonalis. By means of particle distribution technique blood flow was measured in 25 different organs. By additional determination of arterio-venous O2 difference (AVDO2) between heart and brain oxygen consumption could be calculated. All data were measured before, 15, 30, 45 and 60 min after injection of 0.05 or 0.1 mg/kg, respectively, N-carboxy-3-morpholino-sydnonimine ethylester (molsidomine, Corvaton) i.v. 1. Molsidomine reduces blood pressures in all parts of the circulation measured. The duration of effects exceeds the experimental period. 2. The compound is no coronary vasodilator in the dose range selected, no dilation of cerebral occurs. Blood flow in kidneys remains constant. Blood flow values of all other organs do not give any indication of an essential peripheral dilatory effect of the drug. 3. Oxygen consumption of left ventricle is significiantly reduced by 25% with molsidomine (0.05 mg/kg i.v.). Oxygen consumption of brain remains constant. 4. All data are in accordance with the hypothesis that molsidomine exerts its effect predominantly by acting on capacitance vessels (venous pooling) of the circulation.

Anesthesia↗
PubMed1976

[The effect of carbocromen on cardiac cyclic adenosine-monophosphate].

The coronary-active drug 3-2-diethylaminoethyl)-4-methyl-7-(carbethoxy-methoxy)-2-oxo-1,2-chromene-hydrochloride (carbocromen, Intensain) is known to be an inhibitor of phosphodiesterase (PDE). After intravenous as well as after intraduodenal application of therapeutic doses carbocromen increases in vivo the cAMP-contents of the hearts of rats (by up to 30%) and dogs (up to 50%). This effect is dose related. Correlations between the pharmacokinetic properties and metabolic actions of carbocromen and its influence on the adenylcyclase system are discussed.

Animals↗
PubMedDate not supplied

Molsidomine: alternative approaches to treat myocardial ischemia.

The long-acting antianginal drug molsidomine has been shown experimentally to reduce myocardial infarct size when administered prior to or after cardiac insult. This is due to several drug actions. Dilation of postcapillary capacitance vessels diminishes venous return, preload, heart dimensions, and myocardial oxygen consumption. Relaxation of stenosed conductive coronary arteries increases the perfusion of myocardial areas at risk of infarction due to enhanced collateral circulation. Increased regional blood supply nourishes predominantly subendocardial cardiac muscles as a result of reduction of extravascular coronary pressure, and resistance. The stable heart rate and cardiac contractility favor improved heart performance. The inhibition of platelet aggregation in vivo by molsidomine or its active metabolites, SIN-1 and SIN-1A, is linked to the stimulation of prostacyclin synthesis, inhibition of thromboxane release with induction of thrombosis and vasoconstriction, and enhanced concentrations of cyclic guanosine monophosphate. Dilation of coronary arteries after intracoronary administration of SIN-1, with inhibition of platelet aggregation by restrained release of adenosine diphosphate and stabilization of platelet membranes, facilitates the recanalization of stenosed arteries and reduces coronary muscle tone at the site of thrombosis. Activation of the human fibrinolytic system and drug-induced release of a plasminogen activator favor dysaggregatory effects. The drug's inhibiting actions on lipoxygenase products of arachidonate (e.g., 12-hydroperoxy-eicosatetraenoic acid and leukotrienes) may shift prostaglandin catabolism to cyclooxygenase products (e.g., prostacyclin) that protect against the expansion of ischemia and the induction of coronary spasm. Experimentally, the hemodynamic effectiveness of molsidomine can be antagonized by catecholamines (afterload effects) and dihydroergotamine (preload and afterload effects) respectively. Further clinical investigations will clarify the application of these mechanisms for the therapeutic success of the drug in human myocardial infarction.

Cardiovascular System↗
PubMedDate not supplied

Comparison of cardiac and hemodynamic effects of platelet-activating factor-acether and leukotriene D4 in anesthetized dogs.

In anesthetized dogs, platelet-activating factor-acether (PAF; 0.2-1.6 micrograms/kg) and leukotriene (LT) D4 (0.5, 1, and 3 micrograms/kg) were injected into the left circumflex (LCX) coronary artery. Cardiac and systemic hemodynamics, and the ECG were continuously recorded. PAF reduced cardiac performance and affected hemodynamics in a dose-dependent manner: At 7 +/- 3s, LCX flow initially increased by 40%-172% followed by a reduction of 43%-100%, and coronary diameter (measured with ultrasonic techniques) decreased by 4%-10%. Total and late coronary resistance increased. Left ventricular (LV) systolic pressure fell by 22%-48% and LV filling pressure decreased by 5 mm Hg after 0.8 microgram/kg PAF. The LVdP/dtmax diminished by 38%-47%. Peak blood pressure reduction (35%) occurred 60 s after PAF application and lasted for 1.4 min. Heart rate decreased by 10%-17% at peak PAF actions. LTD4 reduced LCX flow by 38%-87%, and coronary diameter by 5%-12%, returning to control value within 3.4 min. Blood pressure, LV pressure, and LVdP/dtmax decreased while heart rate and LV filling pressure increased. ST segments and R-wave voltage of the ECG in lead II elevated after either compound although the effects were more pronounced after LTD4. Indomethacin (5 mg/kg i.v.) pretreatment did not affect LTD4 actions on cardiohemodynamics, but the putative leukotriene antagonist FPL 55712 (1 mg/kg i.v.) blocked LTD4 actions on the heart and circulation. PAF influences on LCX flow were modified by indomethacin: initial flow rose by 250%, and coronary diameter fell by 12%, followed by sustained flow and diameter reduction during the second phase on PAF action. FPL 55712 did not affect the early flow increase after PAF but attenuated the later flow reduction, which was blocked by indomethacin. Thus, PAF and LTD4 may have effects on canine conduit arteries besides their effects on the coronary resistance vessels. The circulatory derangement after PAF may be aggravated by additional eicosanoid release. PAF and LTD4 may be involved in coronary blood flow variations and negative inotropy accompanying anaphylactic disease state.

Animals↗
PubMedDate not supplied

Prostacyclin prevents ventricular fibrillation in a canine model of sudden cardiac death.

The antifibrillatory, antithrombotic and hemodynamic properties of intraventricular prostacyclin (PGI2) application were studied in conscious canine model of sudden cardiac death. In anesthetized dogs, a wire electrode was implanted into the left circumflex coronary artery (LCX) and acute myocardial ischemia was produced by 90 min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. An intracardiac pressure transducer measured ventricular pressure, heart rate, filling pressure and dP/dt. The ECG was obtained from subcutaneous chest needles. Six days later while in ambulatory state, a 180 microA DC current was applied for 4 h to the LCX intimal lining in Tris-HCl (n = 10) and PGI2-treated dogs (50 and 100 ng/kg/min, 11 and 12 dogs, respectively). Myocardial injury and coronary thrombosis induced by electrical stimulation produced ventricular fibrillation in all vehicle-treated dogs at 145 +/- 33 min (mean +/- S.D.). In PGI2-treated hearts only 2 animals fibrillated at 150 +/- 29 min and 180 +/- 52 min following 50 and 100 ng/kg/min of the prostanoid, respectively. Thus, 18/23 PGI2-treated dogs survived 4 h electrical stimulation of the artery. Within the LAD perfusion zone infarction was observed of equal volumes in vehicle and PGI2-treated animals. No ischemia occurred distal to the LCX coronary thrombosis. Ventricular pressure fell in all groups. Heart rate increased in the controls and those animals treated with 50 ng/kg/min PGI2 while 100 ng/kg/min PGI2 increased heart rate by 22 +/- 5% (p less than 0.05). Filling pressure increased in controls but fell in the PGI2-treated hearts. The results indicate that PGI2 can prevent ventricular fibrillation resulting from acute ischemia at a site distant to previous myocardial ischemia with superimposed intimal injury and coronary thrombosis. The PGI2 properties are due to prevention of coronary thrombosis and the occlusion of the artery. Antifibrillatory effects of the prostanoids are suggested.

Animals↗
PubMedDate not supplied

The effects of oral nafazatrom (= BAY g 6575) on canine coronary artery thrombosis and myocardial ischemia.

The in-vivo effects of the new antithrombotic compound nafazatrom on experimental thrombosis of the left circumflex coronary artery, on hemodynamics and on ultimate infarct size were studied in pentobarbital-anesthetized, open-chest dogs. Coronary artery thrombosis was induced by low amperage stimulation (150 microA, DC for 6 hr) of the circumflex artery intimal lining. The effects of oral pretreatment of 1%-Tylose suspension as drug diluent and 5 mg/kg nafazatrom plus vehicle were determined. Both agents were administered twice a day before onset of current stimulation. In the drug vehicle group, coronary thrombosis caused severe hemodynamic alterations, e.g. blood pressure and left ventricular pressure decrease, as well as reduction in the LV dP/dtmax associated with increases in end-diastolic filling pressure and heart rate. Time to coronary artery occlusion was delayed by nafazatrom (5.2 +/- 1.1 vs 3.1 +/- 0.4 hr, p less than 0.05). Smaller blood pressure and LV dP/dtmax reductions and minor heart rate and filling pressure increases around the time of thrombus formation suggested cardioprotection with the drug. Smaller R wave changes and S-T segment elevation indicated minor ischemia at the time of occlusive coronary artery occlusion in nafazatrom-treated hearts (24 +/- 0.5 vs 72 +/- 7% ST segment elevation, p less than 0.01). Thrombus wet weight was 18.4 +/- 2.6 mg in the nafazatrom group, but 63.7 +/- 3.1 mg in controls (p less than 0.01). Thus, ultimate infarct size was smaller in nafazatrom-treated hearts as related to left ventricular mass (8.4 +/- 1.4 vs 32.3 +/- 3.1%, p less than 0.02) or to the occluded artery perfusion area at risk for infarction (16 +/- 3.4 vs 53 +/- 6.2%, p less than 0.05). No ex-vivo effect of nafazatrom on collagen-induced platelet aggregation was observed. These results may indicate efficacy of the drug in prevention of acute coronary artery disease as one cause of ischemic jeopardy of the myocardium and/or therapeutic value in coronary artery spasm.

Animals↗
PubMedDate not supplied

Effects of prostacyclin (PGI2) and adenosine (ASN) on total and regional blood flow of isolated, collateralized dog hearts.

Dogs were subjected to chronic occlusion of the left circumflex and the right coronary artery by ameroid-type constrictors 4-5 weeks before the experiments. The hearts were isolated, fibrillated and perfused with blood (100 mm Hg) from a support dog. Total and regional myocardial blood flow as well as peripheral coronary pressure (circumflex artery) were determined before and during infusion of PGI2 and ASN into the isolated hearts. Both drugs increased total and regional blood flow to all parts of the myocardium in a dose-dependent manner, PGI2 being 2-3 times more potent than ASN. The perfusion pressure for the collateral-dependent myocardium, the peripheral coronary pressure, decreased following high doses of both drugs. For PGI2 a dose level existed where total flow was increased, while peripheral coronary pressure remained unaffected. After termination of the infusion of PGI2, a peripheral coronary pressure rose above predrug level with the total blood flow still being elevated. These findings indicate a PGI2-induced dilatation of collateral vessels. In general, the hemodynamic profile within the isolated hearts and the support dogs was characterized by the pronounced vasodilatory effects of PGI2 on arterioles. However, these effects did not deteriorate further the non-homogenous blood flow distribution in the collateralized portions of the myocardium.

Adenosine↗
PubMedDate not supplied

Effects of molsidomine on the coronary circulation in anesthetized dogs.

The intravenous effects of molsidomine on the coronary circulation, myocardial oxygen consumption, and hemodynamics were investigated in anesthetized, open-chest dogs. Left coronary artery flow was reduced after drug administration, while coronary resistance remained unaffected. The coronary arteriovenous oxygen difference did not change after molsidomine. Myocardial oxygen consumption was significantly reduced. Stroke work of the heart was diminished. Molsidomine caused a dose-dependent decrease in aortic and left ventricular pressures (after-load) as well as a sustained fall in left ventricular end-diastolic and mean pulmonary artery pressures (preload). Heart rate and contractility were only moderately affected. Stroke volume and cardiac output decreased significantly for the experimentation time, while total peripheral resistance increased after 0.25 mg/kg molsidomine. All observed effects of the drug can be explained by extracardiac effects: an increase in venous capacity. No direct effects of molsidomine on myocardial function could be noted. The fall in blood pressure was not induced by vasodilatation of peripheral arteriolar vessels but occurred as sequel of the reduced cardiac output following decreased ventricular filling. Molsidomine improved the oxygen supply-demand balance by decreasing external work of the heart and hence myocardial oxygen demand.

Anesthesia↗