Biomedical subjects

V B Fiedler

Publications and source records attributed to V B Fiedler.

64 records · Page 4Linked to original sources

PubMedDate not supplied

Thrombolytic effects of intracoronary streptokinase on canine coronary artery thrombosis.

The thrombolytic and hemodynamic properties of intracoronary streptokinase (SK) application were studied in an in-vivo canine model with left circumflex coronary artery thrombosis, initiated by electrical stimulation (150 microA, DC for 6 h) of the artery's intima via an implanted silver wire. In pentobarbital-anesthetized, open-chest dogs acute myocardial ischemia was determined by a dehydrogenase-dependent staining of the coronary artery perfusion area. Thrombus weight was determined post-mortem. Saline-treated control animals developed coronary thrombosis after 3.1 +/- 0.4 h of stimulation. Thrombus weight was 64 +/- 3.1 mg. Acute infarct volume was 32 +/- 3.1% of total left ventricle, and 53 +/- 6.2% of the coronary artery risk region for infarction. At occlusive thrombosis, blood pressure, ventricular pressure and the LV dP/dtmax fell significantly, whereas heart rate and the end-diastolic filling pressure increased. Severe ST-segment elevation and loss of R wave voltage indicated myocardial ischemia. At 20 min into thrombotic vessel occlusion, 2,000 IU/min SK were infused by way of a Sones-catheter advanced to the thrombus. Coronary thrombosis consistently lysed after 12 +/- 0.7 min of SK infusion, and coronary blood flow as well as hemodynamics were restored. Only minor acute infarction was found indicating viability of ischemic jeopardized myocardium. In another group, the continuous SK-infusion (20 IU/kg/min) concomitant with electrical vessel stimulation prevented coronary thrombosis and acute ischemia, and no significant hemodynamic alterations were noted. These results indicate that intracoronary SK-infusion can lyse acute thrombosis as sequel of electrical stimulation. This prevents development of acute myocardial infarction. Continuous SK-infusion can completely prevent coronary thrombosis in response to intimal injury.

Animals↗

PubMedDate not supplied

Effects of oral carbocromene pretreatment on infarct size following experimental coronary artery occlusion.

This study examines the acute effects of the antianginal drug carbocromene (chromonar) in dogs (20 mg/kg p.o., twice daily for 8 weeks) on mortality, hemodynamics, coronary collateral blood flow, and myocardial infarct size. Following the chronic pretreatment and during acute phase of the experiments, the animals received an intravenous bolus of 4 mg/kg of carbocromene 15 min prior to left anterior descending coronary artery occlusion, and 40 micrograms/kg/min as an infusion during occlusion and reperfusion. Total mortality 2 days postocclusion was 50% in saline control experiments but 20% in carbocromene-treated animals (p less than 0.05). Hemodynamics were not significantly changed during drug administration except for a significant ST-segment elevation during vessel occlusion. Coronary collateral blood flow increased after carbocromene treatment by 30% (p less than 0.05) in the ischemic endocardial region and by 60% (p less than 0.02) in the border zone of the area at risk of infarction. Flow in nonischemic myocardium did not change so that "coronary steal" was not observed. At reperfusion, a flow increase occurred in the ischemic and border zones. Myocardial infarct size was 24% smaller after carbocromene than in control animals (p less than 0.02) when compared to the AR, and 46% smaller (p less than 0.01) in relation to the total left ventricle. We conclude that carbocromene administered orally before acute coronary artery occlusion and intravenously during occlusion and subsequent reperfusion can reduce infarct size by salvage of lateral and subepicardial border zones.

Administration, Oral↗

PubMedDate not supplied

Effects of catecholamines on cardiovascular actions of molsidomine in anesthetized dogs.

We measured over a 2-h period the effects of molsidomine (0.5 mg/kg i.v.) on pulmonary artery and left ventricular (LV) end-diastolic pressures and internal heart dimension (preload), LV systolic and peripheral blood pressures and total peripheral resistance (afterload), and heart rate, LV dP/dt, stroke volume, and cardiac output (heart performance) of dogs anesthetized with pentobarbital. The hemodynamic effects of molsidomine were influenced by intravenous infusion of 0.10 or 0.20 micrograms/kg/min norepinephrine or 3 or 6 micrograms/kg/min dopamine. Molsidomine decreased preload, stroke volume, and cardiac output for over 2 h and ventricular and peripheral pressures for 45 min. Peripheral resistance, heart rate, and LV dP/dtmax were not altered. Low doses of norepinephrine and dopamine reversed the effect of molsidomine on afterload. However, neither catecholamine influenced the reduced end-diastolic filling pressure after molsidomine. The diminished stroke volume was elevated by either catecholamine so that cardiac output eventually increased. These results indicate that both norepinephrine and dopamine can reverse the certain effects of intravenously administered molsidomine, probably by increasing cardiac contractile force, cardiac output, and peripheral resistance. A combination of molsidomine's preload lowering effects with dopamine's effects on afterload may be useful for the treatment of patients with myocardial failure.

Anesthesia↗

PubMedDate not supplied

Reduction of acute myocardial ischemia in rabbit hearts by nafazatrom.

The effects of oral nafazatrom pretreatment (10 mg/kg, twice a day, for 10 days) on myocardial ischemia were studied in the rabbit heart during 6-h occlusion of the left anterior descending coronary artery (LAD). The tension-time index (TTI), hemodynamics, and ischemia size were determined (Evan's blue-triphenyltetrazolium chloride staining with planimetry). In drug-vehicle controls, left ventricular (LV) and peripheral pressures and LV dP/dtmax decreased, while heart rate, end-diastolic pressure, the TTI, and electrocardiographic ST segments increased. Hemodynamics were nearly unaltered in the nafazatrom-pretreated animals, except for a heart rate elevation during the initial phase of LAD occlusion. In drug-treated hearts, 45 +/- 6% of the LAD perfusion region at risk was ischemic, showing a patchy distribution. In vehicle controls, 82 +/- 4% (p less than 0.02 vs. nafazatrom pretreatment) of the LAD-perfused myocardial regions was transmurally ischemic, showing a uniform pattern. Thus, nafazatrom pretreatment prevented most hemodynamic changes following LAD occlusion in the rabbit heart. Significant amounts of the muscle remained normoxic within the nonperfused arterial regions. These results indicate that the inhibition of lipoxygenase enzymes by nafazatrom may delay the development of ischemic damage to the heart following acute coronary artery occlusion.

Acute Disease↗

PubMedDate not supplied

Cardioprotective effects of carbocromen in awake and anesthetized dogs with amitriptyline poisoning.

We studied the effects of the antianginal drug carbocromen (4 mg/kg bolus plus 80 micrograms/kg/min i.v.) on amitriptyline (400 micrograms/kg/min i.v.) toxicity. In anesthetized dogs, amitriptyline increased heart rate, left ventricular (LV) end-diastolic pressure, and the PR and QT intervals, the QRS complex, and the S-T segments of the peripheral electrocardiogram. Blood pressure, LV pressure, and LV dP/dtmax fell considerably. Survival time was 37 +/- 4 min in amitriptyline-treated dogs and 64 +/- 3 min (p less than 0.05) in those receiving amitriptyline plus carbocromen. The amount of amitriptyline consumed until death increased from 14.8 to 25.6 mg/kg (p less than 0.05) with carbocromen. In conscious dogs, the hemodynamic impact of intraatrial amitriptyline was similar to that in anesthetized animals, and changes in stroke volume resembled those of dP/dt. Cardiac output was not altered, and peripheral resistance decreased moderately. Carbocromen prevented most of the typical amitriptyline effects on the heart and circulation. Sustained ventricular arrhythmia occurred at 29 +/- 4 min with amitriptyline infusion but was delayed to 58 +/- 3 min (p less than 0.05) when carbocromen was added. These experiments demonstrate (a) amitriptyline intoxication produced ventricular tachyarrhythmia and cardiac failure if high agent concentrations were achieved; (b) these rhythm disorders were associated with slowing of intraventricular conduction, which could be enhanced by carbocromen; and (c) carbocromen might be an effective therapy for amitriptyline-caused arrhythmia with cardiovascular collapse.

Amitriptyline↗

PubMedDate not supplied

Protection by carbocromene and molsidomine against arrhythmias occurring during coronary artery occlusion and reperfusion in dogs.

We studied the effects of carbocromene (4 mg/kg plus 40 micrograms/kg/min i.v.) and molsidomine (0.1 mg/kg plus 2 micrograms/kg/min i.v.) on arrhythmias occurring during 90-min occlusion and 30-min reperfusion of the left anterior descending coronary artery in anesthetized dogs. Both drugs reduced the incidence of left ventricular (LV) premature depolarization during ligation (39% after carbocromene and 33% after molsidomine vs. 80% in controls; both p less than 0.05) and tachycardia (44% after carbocromene and 38% after molsidomine vs. 85% in controls; p less than 0.05). During reperfusion, the incidence of LV fibrillation was reduced in the carbocromene- (6 vs. 38% in controls; p less than 0.05) and molsidomine-treated dogs (10 vs. 38% in controls; p less than 0.05). The high incidence of ectopic activity and the ST segment elevation occurring after coronary ligation in control animals were prevented by both drugs. The hemodynamic deterioration after coronary occlusion, i.e., increase in blood pressure, LV systolic and end-diastolic pressures, LV dP/dtmax, and tachycardia observed in controls, was prevented by carbocromene. Molsidomine reduced blood pressure and LV pressure by 18 and 27% (p less than 0.05), respectively, during coronary occlusion. During reperfusion, no hemodynamic alterations occurred in the drug-treated animals. We conclude that carbocromene reduced the electrophysiologic consequences of acute ischemia by hemodynamic and anti-ischemic effects on heart metabolism. Molsidomine protected the jeopardized heart by a similar attenuation of hemodynamic derangement after coronary occlusion and perhaps by influencing prostanoid release from the ischemic myocardium.

Anesthesia↗

PubMedDate not supplied

Effects of nafazatrom and indomethacin on experimental myocardial ischemia in the anesthetized dog.

The anti-ischemic effects of nafazatrom (10 mg/kg intraduodenally) have been studied in a canine model of myocardial infarction. Nafazatrom was given 30 min before and 2 h after occlusion of the left anterior descending coronary artery (LAD). Effects were compared with those after intravenous indomethacin (10 mg/kg) treatment. Infarct size was measured at 6 h of coronary occlusion by postmortem tetrazolium staining. Myocardial ischemia was reduced after nafazatrom administration, whether related to total left ventricle (18 +/- 3.3 vs. 30.7 +/- 4.8%; p less than 0.05) or to the LAD vessel area at risk for infarction (51.4 +/- 4.0 vs. 82.5 +/- 4.5%; p less than 0.01). Salvage with nafazatrom occurred in the subepicardial and endomural tissues without lateral protection. Indomethacin had no effects on infarction. The LAD occlusion-induced hemodynamic consequences were reduced at 15 min by nafazatrom and remained unchanged by indomethacin. During the following experimental course, no differences were noted between the groups. At 6 h, blood flow in the nonoccluded circumflex artery increased by 12.6 +/- 3.2 ml/min (p less than 0.05) following nafazatrom treatment. Thus, nafazatrom reduced ischemia by a mechanism unrelated to changes in hemodynamics. Most likely, this was due to 5-lipoxygenase inhibition. This may shift arachidonic acid metabolism to cyclooxygenase products and prevent release of deleterious lipoxygenase products by neutrophils during ischemic injury.

Anesthesia↗

PubMedDate not supplied

Influences of cardiovascular drugs on leukotriene D4 action.

In anesthetized dogs, the effects of intracoronary leukotriene D4 (LTD4) (0.5 micrograms/kg) were studied on hemodynamics, the electrocardiogram (ECG) (lead II), flow in the left circumflex (LCX) coronary artery, and resistance in the absence or presence of intravenously administered cardiovascular drugs: nifedipine (10 micrograms/kg), nitroglycerin (5 micrograms/kg/min), isosorbide dinitrate (100 micrograms/kg), molsidomine (500 micrograms/kg), propranolol (500 micrograms/kg), and phentolamine (250 micrograms/kg). LTD4 increased left ventricular end-diastolic pressure (LVEDP) by 126% (p less than 0.01), the S-T segments of the ECG from 0.3 to 2.4 mV (p less than 0.001), and coronary resistance from 3.5 to 35.7 mm Hg X min X ml-1 (p less than 0.001). LCX blood flow fell from 33.8 to 3 ml/min (p less than 0.001), and LV dP/dtmax decreased by 51% (p less than 0.05). Nitroglycerin and isosorbide dinitrate were ineffective on cardiovascular LTD4 actions. Nifedipine and molsidomine inhibited the coronary flow reduction with LVEDP and S-T segment elevation by the LTD4 vasoconstriction. Negative inotropic LTD4 effects were counteracted by molsidomine. Phentolamine augmented the degree and duration of coronary constriction after LTD4. Propranolol weakened the coronary and circulatory eicosanoid actions. Indomethacin (5 mg/kg, i.v.) neither abolished the LTD4-caused hemodynamic and electrocardiographic consequences, nor attenuated beneficial nifedipine or molsidomine antagonism. Thus, it can be considered that nifedipine may inhibit the Ca2+ influx required for the effects of exogenously administered LTD4. LTD4 apparently does not act over cardiac alpha- or beta-receptor activation. Molsidomine effects on cardiohemodynamics with platelet and coronary vascular eicosanoid actions may protect the heart against LTD4 induced derangement.

Animals↗

PubMedDate not supplied

Effects of nifedipine and indomethacin on leukotriene C4- and D4-induced coronary constriction at normal and reduced coronary perfusion in dogs.

The effects of intracoronary leukotriene C4 (LTC4) and D4 (LTD4) (both 0.1 microgram/kg) were studied in 23 anesthetized open-chest dogs at normal (= mean aortic pressure) and reduced (51 +/- 2 and 32 +/- 2 mm Hg) coronary perfusion pressures. The left anterior descending coronary artery was cannulated and blood flow measured. Subendocardial fiber segment length was obtained with ultrasonic crystals. At normal coronary perfusion pressure, LTC4 and LTD4 reduced coronary blood flow from 81 +/- 6 and 78 +/- 7 ml/min per 100 g by 41 +/- 4% and 41 +/- 4% (both p less than 0.0005), respectively. However, segment length shortening was not depressed by LTC4 or LTD4. At reduced coronary perfusion pressure, LTC4 and LTD4 diminished coronary blood flow from 35 +/- 5 and 32 +/- 3 ml/min per 100 g, by 28 +/- 5% (p less than 0.0025) and 30 +/- 5% (p less than 0.005). Thus, reduction of coronary blood flow was less by both LTC4 (p less than 0.01) and LTD4 (p less than 0.05) at reduced rather than at normal coronary perfusion pressure. Segment length shortening was depressed by LTC4 from 6.5 +/- 1.2% to 2.4 +/- 1.6% (p less than 0.05) and by LTD4 from 5.6 +/- 1.4% to 3.1 +/- 0.9% (p less than 0.05), respectively. Indomethacin (5 mg/kg, i.v.) and nifedipine (10 micrograms/kg, i.v.) did not abolish the LT-induced coronary artery constriction. However, in animals pretreated with indomethacin or nifedipine, reduction of coronary blood flow by LTs was not attenuated at reduced coronary perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Effect of BAY U 3405, a new thromboxane antagonist, on sudden death in rabbits.

We studied the effects of BAY U 3405 in experimental models of arachidonic acid- and collagen-induced sudden death. BAY U 3405 was effective in dose-dependently inhibiting death from both arachidonic acid and collagen at doses of 1, 3 and 10 mg/kg orally. The survival rate, usually amounting to less than 10% in vehicle-treated animals, was dramatically increased to 100% at the highest dose. The data obtained emphasize the role of thromboxane A2 as a mediator in this model, and the potential usefulness of BAY U 3405 for thromboembolic disorders.

Animals↗