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Biomedical subjects

R Sievers

Publications and source records attributed to R Sievers.

At least 55 records · Page 3Linked to original sources
PubMed1985

Magnetic resonance imaging of acute myocardial infarction using a nitroxyl spin label (PCA).

The effects of an intravenously administered nitroxyl spin label (PCA) on the magnetic resonance imaging (MRI) appearance and relaxation times of acute canine myocardial infarctions were studied. Twenty-four hours after ligation of the left anterior descending coronary artery (LAD), animals were either sacrificed immediately (three dogs) or injected with 3.0 mmol/kg of PCA prior to sacrifice (six dogs). The PCA group dogs were sacrificed at either 5 minutes postinjection (three dogs) or 15 minutes postinjection (three dogs). Magnetic resonance imaging (0.35 T) using spin-echo techniques demonstrated high signal intensity in the infarct relative to normal myocardium in all three groups. In the control group, the T1 and T2 relaxation times were longer in infarcted compared with normal myocardium, but only the measure in T2 reached statistical significance (P less than .05). PCA produced infarct-avid T1 shortening in the six dogs that received it. Contrast in the group sacrificed at 15 minutes postcontrast administration was greater than that in the control group due to T1 shortening in the infarct. Thus, PCA produces differential effects on normal and infarcted myocardium. Between 5 and 15 minutes after IV administration, it causes greater changes in the infarct due to prolonged retention in this region.

Animals↗
PubMed1984

Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit.

Seventy-two rabbits were separated into groups to receive no drug, subcutaneous verapamil, metoprolol, hydralazine, metoprolol and hydralazine, or oral verapamil in 1 of 3 doses daily for 10 weeks. They also received a high-cholesterol diet and had serum triglyceride, cholesterol, and verapamil levels measured twice during the study. Blood pressure (BP), heart rate and weight were measured every 10 days. Approximately 60% of the rabbits given verapamil had detectable levels of the drug in their serum. This group had significantly less severe atherosclerosis in their aortas at the time they were killed, even though they had significantly higher cholesterol levels than the other groups. This group also did not have different BP than the other groups (except for the subcutaneous verapamil group). Thus, protection from atherosclerosis by verapamil in the cholesterol-fed rabbit is not the result of lowering of BP.

Animals↗
PubMed1984

[Imaging of blood flow-dependent curve parameters in the course of sequential computed tomography of the kidneys following intravenous injection of a contrast bolus].

Since the introduction of fast CT scanners with short scanning times the early density changes observed during the first transit of a contrast bolus can be clearly demonstrated and quantified. A theoretical curve can be fit to the CT data describing the density changes in the kidney according to the indicator dilution principle. A curve parameter can be obtained which characterizes the shape of the curve. Then an image can be calculated which reflects the selected curve parameter rather than tissue densities. Such images have been termed "functional images". Using this type of imaging we were able to demonstrate acute changes in renal perfusion.

Animals↗
PubMed1984

Acute myocardial ischemia: magnetic resonance contrast enhancement with gadolinium-DTPA.

Gadolinium-DTPA (Gd-DTPA) was used to improve the diagnostic utility of magnetic resonance (MR) in detecting early ischemia, before the onset of infarction. Following one minute of left anterior descending coronary artery occlusion, 9 dogs were intravenously injected with either 0.5 mM/kg of Gd-DTPA (6 dogs) or normal saline (3 dogs). One more minute was allowed for perfusion of injectate prior to cardiectomy and MR imaging of the ex situ heart. There was no visible difference in intensity or alterations in magnetic relaxation times between normal and ischemic myocardium in the control (saline-injected) animals. The Gd-DTPA-injected dogs had a well-defined segment of high intensity representing the ischemic myocardium in the anterior wall of the left ventricle, due to significant T2 relaxation rate enhancement in the adjacent normal myocardium. Both T1 and T2 were significantly (p less than 0.01) shortened in the normal myocardium of the Gd-DTPA animals, but relatively greater T2 relaxation rate enhancement resulted in reduced intensity of normal myocardium, thus increasing contrast with ischemic myocardium. As a result of the significant shortening of T1 and T2 in the normal myocardium relative to the ischemic myocardium, improved delineation of the ischemic segment could be obtained using calculated T1 and T2 images. It is concluded that Gd-DTPA has the potential to expand the sensitivity and diagnostic utility of MR in the study of occlusive coronary artery disease.

Animals↗
PubMed1984

Effect of gadolinium-DTPA on the magnetic relaxation times of normal and infarcted myocardium.

Acute myocardial infarctions were produced in 11 dogs by ligation of the left anterior descending coronary artery. Twenty-four hours after ligation, 0.35 millimoles per kilogram of Gd-DTPA was injected intravenously, followed by cardiectomy either 90 seconds (3 dogs) or 5 minutes (5 dogs) later. The remaining 3 dogs had cardiectomy without injection of Gd-DTPA at 24 hours after coronary occlusion. The 3 dogs that did not receive Gd-DTPA had longer T1 and T2 relaxation times in infarcted myocardium than in normal myocardium, as measured by a 10.7-MHz magnetic resonance (MR) spectrometer. The T1 and T2 relaxation times of normal myocardium at 90 seconds postinjection of Gd-DTPA were significantly shorter (p less than 0.05) than those of the normal myocardium of animals that did not receive Gd-DTPA. At five minutes postinjection, significantly (p less than 0.01) greater T1 shortening was exhibited in the infarcted myocardium compared with adjacent normal myocardium in the dogs injected with Gd-DTPA. Thus, Gd-DTPA has differential and time-varying effects on relaxation times of normal and infarcted myocardium.

Animals↗
PubMed1983

Oscillations of cAMP with the cardiac cycle.

Oscillations of cAMP with the cardiac cycle were demonstrated in the rat heart using a stimulator-triggered rapid freeze-clamp to decrease the temperature of the heart from 37 degrees C to -80 degrees C in 5 msec (20,000 degrees/sec) at a predetermined phase of the cardiac cycle. The nucleotide, cAMP, oscillated 60% with the cardiac cycle during normal working conditions, the higher cAMP value occurring during systole.

Animals↗
PubMed1983

Lack of decreased contractility in hearts from atherosclerotic rabbits.

Previous studies have suggested that the contractility of isolated heart muscle removed from rabbits made hypercholesterolemic is decreased. As part of a study evaluating the effects of high-lipid diets on aortic atherosclerosis, we evaluated the contractility of perfused rabbit hearts. Six rabbits were placed on a high-lipid diet for 3 months with cholesterol levels rising to 1700 +/- 400 mg %. After they were killed, their hearts were studied in an isolated, perfused, working heart apparatus at 37 degrees C. Control animals included six rabbits matched for age, six rabbits matched for weight, and six young rabbits. Measurements were made of developed pressure, maximum dP/dt, oxygen extraction, oxygen consumption, and coronary blood flow. There were no significant differences between the contractile parameters of hearts from any group. Since previous studies were conducted with isolated heart muscle at a lower temperature, it may be that hypercholesterolemic effects on membranes may have led to the previous findings of reduced contractility. Our results suggest that hypercholesterolemia, per se, does not decrease cardiac contractility in the rabbit fed a high-lipid diet.

Animals↗
PubMed1983

Nuclear magnetic resonance imaging of acute myocardial infarction in dogs: alterations in magnetic relaxation times.

Nuclear magnetic resonance (NMR) imaging was used to study 24-hour-old acute myocardial infarctions in 8 dogs. Images and measurements of excised hearts were obtained in a 6.5 ml bore-resistive NMR imager (0.35 Tesla). Spin echo NMR imaging in each instance demonstrated the area of infarction as a region of increased signal intensity compared with that in normal myocardium. The T1 and T2 values of the area of infarction were greater than those of normal myocardium in all dogs. For each dog the T1 value was greater for the infarct region; however, the group mean value for T1 (ms) of the infarct region (728 +/- 94) was not significantly greater than that for the normal region (650 +/- 87). The T2 value (ms) was discriminate for all dogs, and the mean value for the infarct region (48 +/- 2) was significantly different (p less than 0.01) from the value for normal myocardium (42 +/- 1). The percent water content of the infarct (79 +/- 1%) was significantly greater (p less than 0.01) than that of normal regions (76 +/- 1%). The linear relationship between T2 value and percent water content showed a good correlation coefficient (r = 0.90; p less than 0.01). NMR imaging detects acute myocardial infarction as a positive image without contrast media. Increased signal intensity of the infarct is related to increased hydrogen density and increased T2 relaxation time.

Animals↗
PubMed1983

Verapamil suppresses atherosclerosis in cholesterol-fed rabbits.

The effect of verapamil, a drug that reduces the concentration of intracellular calcium, on atherogenesis was evaluated in rabbits fed a cholesterol-rich diet for 10 weeks. Ten rabbits received oral verapamil, 8 mg/kg daily; eight received the same oral dose and 0.5 mg/kg daily subcutaneously; nine received oral lanthanum, 35 mg/kg daily, and nine were controls. Over the 10 week period, all groups had average serum cholesterol levels greater than 1,500 mg/dl (normal = 90 +/- 63 mg/dl). At the end of the experiment, the aortas were removed, opened and stained for lipid with Sudan IV. The extent of atherosclerosis was determined by planimetry. The group receiving oral and parenteral verapamil had significantly less atherosclerosis (25 +/- 26% of total intimal area; mean +/- standard deviation), as compared with the controls (73 +/- 24%). Reduction of atherosclerosis with oral verapamil (51 +/- 22%) and lanthanum (59 +/- 31) was not statistically significant. Indexes of contractility in isolated right ventricular papillary muscles (developed tension at maximal length [Lmax] and maximal velocity of shortening [Vmax]) were reduced in the group treated with oral and parenteral verapamil, but not in the others. It is concluded that verapamil suppresses the development of atherosclerosis in rabbits fed a cholesterol-rich diet.

Adenosine Triphosphatases↗
PubMed1983

Verapamil, propranolol, and hydralazine protect against the acute cardiac depression induced by adriamycin.

The apex ejecting isolated rat heart perfused with media containing 3 X 10(-5) mol . litre-1 adriamycin for 40 min demonstrated the following changes in contraction patterns: (a) a ten-fold increase in end-diastolic pressure; (b) a 45% decrease in developed pressure; (c) a 17% decrease in coronary flow; (d) a 27% increase in time to peak pressure; (e) a 26% increase in time for pressure to fall 50% during relaxation; and (f) a 65% decrease in maximum (+) and (-) dP/dt. In rats pretreated 1 h before death, verapamil, propranolol, and hydralazine significantly attenuated the cardiac depression produced by adriamycin. The combinations of verapamil and hydralazine, or propranolol and hydralazine were especially efficacious. Particularly striking was the protection afforded against an increase in diastolic pressure. Digoxin pretreatment afforded no protection. It is postulated that the acute depressive effects of adriamycin may be related to calcium overload.

Animals↗
PubMed1983

A new apex-ejecting perfused rat heart preparation: relation between coronary flow and loading conditions.

The isolated perfused rat heart is an important experimental preparation for both mechanical and biochemical studies. In order to define better the relationship between coronary flow and loading conditions, a new preparation was developed in which the left ventricle ejected through the apex, while the aortic perfusion pressure could be separately controlled at a higher level than the apex afterload. Results were compared with a standard aortic perfused and ejecting preparation. All analyses were made at low calcium concentration (1.6 mmol X litre-1) for reducing cardiac performance. Coronary flow was related to perfusion pressure in the aortic ejecting preparation when the aortic afterload chamber was between 6.0 and 9.3 kPa (45 and 70 mmHg). Coronary autoregulation was demonstrable in the apex ejecting preparation irrespective of the height of the apex afterload chamber and the aortic ejecting preparation when the aortic chamber was between 11.0 and 16.0 kPa (83 and 120 mmHg). Following the addition of 10(-6) mol X litre-1 adenosine, there was significant coronary vasodilatation, and flow became pressure dependent in all cases. In the apex-ejecting preparation, with a high aortic pressure, coronary flow remained at relatively fixed level, and increases in oxygen demand were met by increasing oxygen extraction. Thus, in this preparation oxygen extraction was directly related to workload. With abrupt increases in afterload, going from 6.0 to 9.3 kPa (45 to 70 mmHg) to a higher level, there was evidence of transient hypoxia with the aortic ejecting but not the apex ejecting preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1983

Nuclear magnetic resonance imaging of the infarcted muscle: a rat model.

Eleven Sprague-Dawley rats with experimentally produced infarction of the lower extremities were imaged by nuclear magnetic resonance (NMR) immediately after infarction, and 6 and 24 hours later. Contrast between the infarcted and control muscles was noted immediately and continued to increase through 24 hours. These changes corresponded to a significant increase in the water content of the infarcted extremity at 24 hours. These results suggest promise for NMR imaging in the identification of myocardial infarction and should encourage further investigation in this area.

Animals↗
PubMed1983

The cardiac cycle: regulation and energy oscillations.

Cyclical changes in energy-related metabolites were observed in glucose-perfused but not pyruvate-perfused isolated working rat hearts. A chronological study of various phases of the cardiac cycle indicated maximum changes in metabolites occurred at half time to peak pressure (dF/dtmax). The high-energy phosphates ATP and phosphocreatine, as well as the glycolytic metabolites, glucose 6-phosphate and pyruvate, reached minimum values immediately prior to peak systole and maximum values during late diastole. The products of high-energy phosphate hydrolysis, ADP, inorganic phosphate, and creatine, as well as the regulator, adenosine 3',5'-cyclic monophosphate, showed the phase alternate. It was necessary to study cyclical changes in a maximally stressed glucose-perfused heart because the cyclical changes were small and appeared to be the result of rate-limiting steps in glycolysis and the slow transport of NADH into the mitochondria. For stressing the heart, thereby increasing ATP utilization and augmenting cyclical changes, the afterload chamber was set at 110 mmHg, and the perfusate contained high concentrations of calcium (3.5 mM, free) and isoproterenol (5 X 10(-9) M). When correction was made for binding and compartmentation of metabolites, data indicated that the free energy of ATP hydrolysis was preserved during the contraction process by a continuous binding and recycling of ADP.

Adenine Nucleotides↗
PubMed1983

Energy levels at systole vs. diastole in normal hamster hearts vs. myopathic hamster hearts.

The following studies were carried out to examine energy metabolites and cardiac performance of the failing heart (hereditary cardiomyopathy) of the Syrian hamster (strain UM-X7.1) perfused either by normal or stress conditions, and to determine whether cyclical changes in energy-related metabolites occurred in the glucose-perfused hearts of both normal and heart failure animals. Hamster hearts from 250-day-old animals with moderate heart failure were removed and perfused either as nonworking hearts (Langendorff method, an afterload pressure of 90 mm Hg and 2.5 mM calcium in the perfusate) or as working hearts with stress conditions [an afterload of 110 mm Hg, high calcium concentrations in the perfusate (3.5 mM), and 10(-8) M isoproterenol]. Mechanical parameters (developed pressure and max dP/dt) and measurements of oxygen consumption indicated that both contractility and oxygen consumption had fallen 50% in myopathic hearts, compared with those of normal hamsters perfused with either of the two conditions. By means of a specially designed stimulator-triggered freeze clamp, hearts were terminated at systole and diastole, and tissue content of ATP, ADP, AMP, adenosine, phosphocreatine, creatine, pyruvate, lactate, and inorganic phosphate were analyzed. A 50% reduction in cardiac performance of the cardiomyopathic hamster hearts was associated with a corresponding reduction in systolic ATP, adenosine, and phosphocreatine values, while inorganic phosphate and lactate increased. With glucose as the sole substrate, the high energy phosphates, ATP and phosphocreatine, reached maximum values during diastole and minimum values during systole.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1976

[Birth after a chorionepitheliom with pulmonary metastasis (author's transl)].

We report about a woman, 20 years old, who get a chorionepitheliom with pulmonary metastasis. We treated not by operation but by cytostatics Methotrexat and Actinomycin D over 40 days. The remission of the tumor was significant but accompanied by considerable toxic sideeffects.--18 months after this, we finished a new pregnancy by sectio caesarea without any complications for wife or child.

Cesarean Section↗
PubMedDate not supplied

Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with liposomal amphotericin B (AmBisome).

Systemic fungal infection occurs in 2 to 4.5% of very low birth-weight (VLBW) infants (< 1,500 g) and may be fatal in 25 to 54%. Candida sp. is the major pathogen and amphotericin B the treatment of choice. To reduce side effects and optimize drug action, a formulation of amphotericin B encapsulated in liposomes (AmBisome) has been introduced. Data on 21 VLBW infants who received a full course of AmBisome was collected and its toxic effects with emphasis on nephrotoxicity and hypokalemia assessed. The median gestational age was 25 weeks (range 23-31) with a median birth-weight of 730 g (range 450-1,370). Antifungal therapy was started at a median age of 13 days (range 1-49). The median dose given was 2.6 mg/kg/day (range 1-5), and the median duration of therapy was 28 days (range 11-79), corresponding to a median cumulative dose of 71 mg/kg (range 12-271). Hypokalemia (< 3.0 mmol/l) was observed in 30% before, and 15% during AmBisome treatment. Twenty-one days after the termination of therapy, hypokalemia was not present in any patient. Median maximum daily potassium supplementation did not exceed doses usually recommended for VLBW infants. The median of the maximum creatinine levels before treatment was 121 mumol/l (range 71-221) and fell to 68 mumol/l (range 31-171) during treatment and 46 mumol/l (range 26-62) 21 days after the termination of therapy. All patients treated with AmBisome eradicated fungi and recovered clinically. AmBisome showed no certain nephrotoxicity in VLBW infants in this study.

Amphotericin B↗
PubMedDate not supplied

Cine-CT measurement of cortical renal blood flow.

A modified indicator-dilution technique using radiographic contrast material and a cine-CT scanner was used to measure blood flow in the renal cortex of dogs. To validate this technique, CT measurements were correlated with simultaneous measurements of flow determined by radioactive microspheres. Measurements were taken during euvolemic conditions and after hemorrhage. Thirty-nine measurements were compared, covering a flow range from 1 to 7 ml min-1 g-1, and a good correlation was found between the cine-CT and microsphere results (r = 0.93; p less than 0.001). Additionally, cine-CT measurements were made of the mean transit time (MTT) of contrast material through the renal cortex, and the reciprocal of these MTT values was also well correlated to microsphere determined flow (r = 0.94; p less than 0.001). Thus, cine-CT appears to be a promising new technique for measuring renal blood flow.

Animals↗