Biomedical subjects

R Sievers

Publications and source records attributed to R Sievers.

At least 37 records · Page 2Linked to original sources

PubMed1987

Diltiazem prevents hypertrophy progression, preserves systolic function, and normalises myocardial oxygen utilisation in the spontaneously hypertensive rat.

The effects of diltiazem, a calcium channel blocker, and methyldopa, an adrenergic blocker, on left ventricular hypertrophy and left ventricular function were assessed in spontaneously hypertensive rats and Wistar-Kyoto controls. Diltiazem (30 mg.kg-1/day), methyldopa (400 mg.kg-1/day), or placebo were given with water for six months. Left ventricular function was studied in 12 month old animals using an isovolumetrically contracting heart preparation by measuring maximum developed pressure and myocardial oxygen consumption. Systolic blood pressure was reduced by both drugs but more so by methyldopa. Despite its lesser antihypertensive effect, diltiazem reduced heart to body weight ratios in the spontaneously hypertensive rat to a similar degree as methyldopa (3.4(0.2) and 3.4(0.1) compared with placebo 3.7(0.2), p less than 0.05). Maximum developed pressure increased with methyldopa and diltiazem compared with placebo (188(11) and 200(11) vs 166(11) mmHg, p less than 0.05). Myocardial oxygen consumption was lower in the spontaneously hypertensive rat receiving placebo than in the controls (22.8(3.2) vs 28.3(3.8) ml.min-1.100 g-1, p less than 0.05) and was significantly increased by diltiazem but not by methyldopa (27.9(0.4) vs 24.5(0.6) ml.min-1.100 g-1, p less than 0.05 and NS respectively vs the spontaneously hypertensive rat receiving placebo). Diltiazem and methyldopa normalised the isomyosin composition in the spontaneously hypertensive rat. Myocardial concentrations of energy related metabolites obtained at maximum developed pressure were not different between spontaneously hypertensive rats receiving placebo and controls. However, both diltiazem and methyldopa treated spontaneously hypertensive rats showed a significant reduction in adenosine triphosphate and phosphocreatine and a rise in inorganic phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Magnetic resonance imaging of myocardial infarction using albumin-(Gd-DTPA), a macromolecular blood-volume contrast agent in a rat model.

Magnetic resonance (MR) contrast enhancement of acute myocardial infarction was studied in rats using albumin-(Gd-DTPA), a paramagnetic macromolecule with prolonged intravascular retention after intravenous injection. Histologic examination and distribution measurements of radiolabeled microspheres confirmed induction of regional myocardial infarction after ligation of the left coronary artery. ECG-gated spin-echo images at 2.0 Tesla, employing short, T1-weighted pulse sequence settings, demonstrated time-persistent and significant (P less than .05) enhancement of normal myocardium (66%) and an even greater enhancement of the infarcted area (100%), for as long as 60 minutes after injection of 160 mg/kg albumin-(Gd-DTPA). The contrast difference between normal and infarcted myocardium was increased significantly (P less than .05) after administration of albumin-(Gd-DTPA). The prolonged enhancing effects of albumin-(Gd-DTPA) on MR images are useful for evaluating regional differences in blood volume and capillary integrity between normal and infarcted myocardium.

Animals↗

PubMed1987

Relative carotid blood flow measurements in dogs by high-speed CT. A preliminary study.

A high-speed computed tomography (CT) scanner was used for measuring flow in a phantom and in the common carotid arteries of six dogs. The general ability of the scanner to assess flow using contrast media boluses was tested with the phantom. The validated simple concept was then used in the animals. The carotid blood flow was varied with a distal occluder on one side and measured with electromagnetic flow probes in both vessels. The results are promising and demonstrate a good correlation between the high-speed CT findings and those measured with the flow probes.

Animals↗

PubMed1987

Quantification of effect of pericardium on LV diastolic PV relation in dogs.

The aim of the present study was to quantify the effect of the pericardium on the left ventricular (LV) diastolic pressure-volume relation. The experiments were done in 10 anesthetized closed-chest dogs. Pericardial and cardiac volumes were determined by computed tomography. Pericardial effusion (n = 5) and volume loading (6% dextran iv; n = 5) were used to increase pericardial volume. Volumes were normalized as multiples of the LV volume measured when LV transmural pressure was 6 mmHg (VLV6). Using the data from the pericardial effusion experiments, we calculated the best-fit exponential equations for the pericardial pressure-volume relations. From these equations we calculated that the changes in pericardial volume necessary to shift the LV diastolic pressure-volume curve upward by 2, 5, 10, and 20 mmHg were 0.6 +/- 0.1, 1.1 +/- 0.2, 1.6 +/- 0.2, and 2.2 +/- 0.3 times VLV6, respectively. Using the data from the volume loading experiments, we also calculated the degree of upward shift of the LV pressure-volume relation caused by volume loading, which increased LV mean diastolic pressure by 12 mmHg. (The upward shift is that increment in pericardial pressure caused by the total increase in volume of the extra-LV contents of the pericardium, i.e., the atria, the right ventricle, and any pericardial effusion.) This volume loading increased the total volume of the right ventricle and the atria by 1.0 +/- 0.1 VLV6, which, in itself, increased pericardial pressure by 3.6 +/- 0.8 mmHg. We conclude that in situations in which heart or pericardial volume increases acutely, the pericardium shifts the diastolic pressure-volume relation of the LV upward by a significant amount.

Animals↗

PubMed1987

Factors influencing myocardial response to metabolic acidosis in isolated rat hearts.

We assessed the effects of metabolic acidosis in Langendorff rat hearts to identify factors influencing myocardial response to metabolic acidosis. Intracellular pH (pHi), beta-ATP, phosphocreatine, and inorganic phosphate (Pi) content were measured by 31P nuclear magnetic resonance spectroscopy along with simultaneous measurements of coronary flow and developed pressure during 30 min of perfusion at pH = 6.8, followed by 15 min of reequilibration at pH = 7.4. Under high work-load conditions, pHi, high-energy phosphates, coronary flow, and developed pressure were severely reduced during metabolic acidosis. Each of these hearts exhibited a progressive decline in developed pressure and stopped beating during reequilibration. Lowering work load prevented severe biochemical or mechanical deterioration, allowing complete recovery during reequilibration. In the presence of high work load, factors found to improve myocardial tolerance to metabolic acidosis included maintaining base-line or higher levels of coronary flow with vasodilators or substitution of pyruvate for glucose as the energy-producing substrate. Raising perfusate osmolality did not prevent severe decreases in coronary flow and developed pressure during acidosis, but did allow a dramatic recovery during reequilibration. Recovery of biochemical and mechanical performance after 30 min of metabolic acidosis was directly related to 1) ln[ATP]/[ADP]f[Pi] greater than or equal to 4.1, where [ADP]f is the concentration of free ADP; 2) pHi greater than 6.40; and 3) ATP level greater than or equal to 75% of control.

Acidosis↗

PubMed1987

The preventive effect of verapamil on ethanol-induced cardiac depression: phosphorus-31 nuclear magnetic resonance and high-pressure liquid chromatographic studies of hamsters.

Alcoholic depression of left ventricular function was produced in normal hamsters by the administration of increasing concentrations of alcohol in drinking water (up to 50%) for 6 months. The result was assessed by phosphorus-31 nuclear magnetic resonance of isolated perfused hearts and high-pressure liquid chromatography of freeze-clamped tissues. Hemodynamic data and myocardial oxygen consumption were also monitored. Alcoholic hamsters had significantly higher inorganic phosphate and lower ATP levels, while maintaining normal intracellular pH, phosphocreatine, and creatine. Although coronary flow and oxygen consumption were maintained at normal levels, hamsters ingesting 50% ethanol had significantly lower left ventricular developed pressure and dP/dt. Treatment with verapamil during long-term ethanol consumption prevented the development of these metabolic and functional abnormalities. It is hypothesized that alcohol produces membrane abnormalities leading to adverse ion flux, and that these are largely prevented by concurrent administration of verapamil.

Adenosine Triphosphate↗

PubMed1987

Improved myocardial efficiency in the working perfused heart of the spontaneously hypertensive rat.

We assessed the relationship between determinants of myocardial oxygen demand--wall stress, peak rate of change of pressure and heart rate--and measured myocardial oxygen consumption over a range of loading conditions in the perfused, working heart of 6-month-old spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY). Two isolated heart preparations, an aortic-ejecting heart and an isovolumically contracting preparation with and without isoproterenol (10(-7)M) added, were employed. Under a constant perfusion pressure of 110 mm Hg, the heart rate, developed wall stress, and peak rate of change of pressure were not different between the two groups, but coronary flow and myocardial oxygen consumption were significantly lower in the SHR. Systolic values of myocardial high energy phosphate compounds (adenosine 5'-triphosphate, phosphocreatine) and myocardial lactate in the two preparations were not significantly different between SHR and WKY. Following adenosine infusion at maximum developed pressure (isovolumic preparation), both SHR and WKY demonstrated preservation of coronary reserve. These results indicate that cardiac hypertrophy represents a compensatory adaptation with improved mechanical efficiency in the 6-month-old SHR when maximally stressed and may be related to the shift from V1 to V2 and V3 isomyosin phenotypes that was observed in the hypertensive animals.

Animals↗

PubMed1986

Quantitation of regional myocardial function by cine computed tomography: pharmacologic changes in wall thickness.

To determine the capability of high speed computed transmission tomography to quantitate regional wall thickening dynamics over a wide range of physiologic states, left ventricular wall thickening was studied in nine anesthetized mongrel dogs in the control state and during separate infusions of dobutamine (10 micrograms/kg per min) and phenylephrine (25 micrograms/kg per min). After an intravenous bolus of contrast medium the heart was imaged from base to apex with serial transverse images in eight short-axis cine computed tomographic planes. In each dog during each experimental condition, 50 ms scans spanning the cardiac cycle were acquired at each anatomic level. Left ventricular epicardial and endocardial boundaries were identified on end-diastolic and end-systolic images at the equatorial left ventricular planes by an objective threshold contour method validated in a series of experiments performed on ex vivo anatomic specimens. End-diastolic and end-systolic frames were automatically realigned by superposition of epicardial centers of gravity and then rotated using a cross correlation function. The left ventricular wall thickness was measured manually at 16 points around the circumference by two independent observers. For the group of dogs the average percent wall thickening was 40.5 +/- 28.2% and varied among segments from 18 to 70% in the control state. After dobutamine was administered, significant increases in heart rate and cardiac output (p less than or equal to 0.01) were accompanied by an increase in the average wall thickening (73.6 +/- 51.2%; p less than or equal to 0.001) in the left ventricle; the average wall thickening among segments ranged from 46 to 97%. After phenylephrine administration, significant increases in mean blood pressure and cardiac output (p less than or equal to 0.01) were noted along with a significant increase in average left ventricular wall thickening (60.3 +/- 52.5%; p less than or equal to 0.001). Despite an overall increase in the percent wall thickening, no statistically significant changes in segmental contraction pattern between control and drug intervention states were observed. The wall thickness measurements were highly reproducible between the two independent readers (reliability coefficient = 0.99). Cine computed tomography-derived measurements can potentially be used for quantitative assessment of left ventricular wall thickening dynamics of a single heartbeat during acute interventions, such as the administration of drugs.

Animals↗

PubMed1986

Cardiomyopathic and healthy acidotic hamster hearts: mitochondrial activity may regulate cardiac performance.

A 50% decrease in adenine nucleotides and a 60% decrease in adenosine triphosphate concentration was found in glucose perfused myopathic Syrian hamster heart (240 days old) whereas there was an 18% decrease and 40% decrease respectively in acidotic healthy Syrian hamster heart re-equilibrated with a physiological medium. Correspondingly, there was a 60% decrease in cardiac performance with both models. Developed pressure fell when the phosphorylation potential decreased to less than or equal to 2; however, the heart recovered if mitochondrial activity was activated. If a substrate such as pyruvate or ribose was used with either model cardiac performance returned to near normal, although adenine nucleotide and adenosine triphosphate concentrations were further depressed. With glucose as substrate cardiomyopathic hearts, healthy acidotic hearts, and healthy acidotic hearts re-equilibrated with glucose as substrate had low pyruvate concentrations; limited availability of pyruvate depressed mitochondrial activity. Like the myopathic hearts the re-equilibrated acidotic hearts had high myocardial pyruvate concentrations, above normal ratios of phosphocreatine to creatine, and near normal oxygen consumption, developed pressure, dP/dt, and cyclic adenosine monophosphate concentrations when re-equilibrated with a medium containing pyruvate or ribose as substrate, although adenosine triphosphate and adenine nucleotide concentrations were severely depressed. When adenosine triphosphate values fell from 24 to 2 mumol X g-1 dry weight in the pyruvate or ribose perfused and normal functioning heart the heart stopped beating with no progressive fall in performance before termination of the metabolic processes.

Acidosis↗

PubMed1986

Verapamil preserves adenine nucleotide pool in cardiomyopathic Syrian hamster.

There is a decrease in total adenine nucleotides, cyclic AMP (cAMP), ATP/total ADP, and phosphocreatine (PCr)/creatine (Cr) both in situ and in the perfused heart in the heart failure stage of the cardiomyopathic Syrian hamster. There were decreases in developed pressure, dP/dt, and O2 consumption associated with the decrease in total adenine nucleotides and cAMP. Cardiomyopathic Syrian hamsters (180-240 days old) with congestive heart failure were given water with the calcium entry blocker, verapamil, as an additive 2 mo before death. In the cardiomyopathic group given verapamil the adenine nucleotides, cAMP, and high-energy phosphates were preserved and cardiac performance was not significantly different from that of the verapamil-treated healthy hamsters at the time of death. Pretreatment of cardiomyopathic animals with verapamil (6.6 mg verapamil/ml water consumed by drinking) resulted in significantly higher ATP/total ADP and PCr/Cr compared with nontreated cardiomyopathic hamsters. This is the first report demonstrating that a calcium entry blocker may improve cardiac performance and preserve total adenine nucleotides during the heart failure stage of the cardiomyopathic hamster.

Adenine Nucleotides↗

PubMed1986

Evaluation of the hereditary Syrian hamster cardiomyopathy by 31P nuclear magnetic resonance spectroscopy: improvement after acute verapamil therapy.

The relation between metabolic and functional derangement in various cardiomyopathies has not been well characterized. This information was specifically sought in a spontaneous cardiomyopathic model. Metabolic and hemodynamic parameters were obtained in glucose-perfused beating hearts of 180-200-day-old cardiomyopathic Syrian hamsters and age-matched healthy animals. This period in the cardiomyopathic hamster lifetime is intermediary between the necrotic phase and the appearance of heart failure. We used 31P nuclear magnetic resonance spectroscopy to analyze energy metabolites and intracellular pH. Cardiomyopathic hamsters had significantly higher mole fraction values for inorganic phosphate, lower phosphocreatine mole fraction as well as lower phosphocreatine/inorganic phosphate and adenosine triphosphate/inorganic phosphate ratios. Analysis of pH indicated the presence of regions of increased acidity within the heart of myopathic hamsters. Cardiomyopathic hamsters also had significantly lower left ventricular pressure, coronary flow, and myocardial oxygen consumption. Separate groups of normal and myopathic hamsters were given verapamil for 24 hours (one injection of 4 mg/kg s.c. followed by 1.2 g/l in drinking water). Verapamil-treated myopathic hamsters had evidence of markedly improved mitochondrial function when compared with untreated animals. Left ventricular pressure and coronary flow rose to normal levels. Replacing glucose by pyruvate in the perfusate of myopathic hamsters results in a marked increase in left ventricular pressure, coronary flow, and oxygen consumption with a moderate rise in phosphocreatine. Thus, 180-200-day-old cardiomyopathic hamster heart is characterized by evidence of decreased mitochondrial function, by areas of increased acidity within the heart, and by reduced left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1985

Measurement of cardiac output by cine computed tomography.

High-speed computed transmission tomography (cine CT) is a new noninvasive technique that may be useful for the rapid, accurate quantitation of cardiac function. The capability of cine CT to assess cardiac output was examined 10 mongrel dogs as an initial step in validating this method. After the dogs were anesthetized, femoral arterial pressure and pulmonary artery thermodilution catheters were inserted. After intravenous injection of a bolus of contrast medium, cine CT scans were performed in the flow mode, in which 50-ms scans were triggered electrocardiographically at end-diastole at 8 levels during sequential cardiac cycles. Scans and thermodilution measurements of cardiac output were obtained at rest and during altered hemodynamic states induced by separate infusions of dobutamine and phenylephrine. Time-density analysis was performed over the left ventricular cavity and curves were fitted to the CT flow data by gamma-variate analysis. Using the Stewart-Hamilton equation established for indicator dilution techniques, the cardiac output was calculated. The results established a direct linear correlation (r = 0.92) between cine CT cardiac output and thermodilution cardiac output over a wide range of cardiac outputs (1.5 to 6.3 liters/min). This study demonstrates that cine CT can provide a reliable estimate of cardiac output noninvasively using contrast medium as an indicator in dogs.

Cardiac Output↗

PubMed1985

Influence of myocardial isomyosins on cardiac performance and oxygen consumption.

There was 21% isomyosin V1 in the 12 month SHR (Spontaneous Hypertensive Rat) and 70% isomyosin V1 in the 6 month WKY (Wystar-Kyoto), nevertheless there was no difference in maximum developed pressure nor maximum dP/dt in the isovolumically beating hearts of the two sets of animals. [Hearts were perfused with hypercalcemic perfusate in the presence of isoproterenol (10(-7)M)]. There was, however, a a 32% reduction in oxygen consumption per gram of dry weight per beat in the 12 month SHR as compared to the 6 mo WKY. Associated with a shift towards isomyosins V2 and V3 in the 6 and 12 month WKY and SHR there was no corresponding change in maximum dP/dt nor developed pressure, but there was a conservation in oxygen consumption.

Aging↗

PubMed1985

In vivo assessment of left ventricular wall and chamber dynamics during transient myocardial ischemia using cine computed tomography.

Using a new computed tomographic (CT) scanner design that uses a rapidly moving focused electron beam, 50-ms CT scans were obtained at 2 axial levels simultaneously through the hearts of 6 dogs in order to analyze left ventricular (LV) wall thickness and cross-sectional chamber area after acute occlusion of the left anterior descending coronary artery (LAD). Ten or fifteen 50-ms CT scans (rate of 17 scans/s through the middle of the left ventricle were performed in 1 second (cine acquisition) during intravenous administration of contrast medium at rest, 60 seconds after acute occlusion of the LAD, and 60 seconds after release of the occlusion. The percent extent of systolic wall thickening of the potentially ischemic anterior segment was 37 +/- 15% (+/- standard deviation) in the control state and -5 +/- 6.5% during LAD occlusion (p less than 0.01). There was no significant difference in the percent change in LV luminal area from end-diastole to end-systole between the control state (50 +/- 19%) compared with LAD occlusion (47 +/- 21%). There were no significant differences in the extent of systolic wall thickening or LV luminal area between the control state and 60 seconds after release of occlusion. The alterations in regional myocardial function during acute ischemia are characterized by wall thinning during systole in the jeopardized segment and no significant change in global LV function. These features can be assessed by cine computed tomography during a solitary heart cycle.

Animals↗

PubMed1985

Modification of experimental atherosclerosis by calcium-channel blockers.

The process of atherosclerosis, although not completely understood, is being clarified. A unifying hypothesis holds that the initial event is endothelial injury, followed by platelet aggregation and release reactions. This leads to smooth muscle cell migration into the intima and replication, with subsequent secretion of elastin, collagen and glycosaminoglycans (which binds lipids). Several animal studies have shown that calcium plays an important role in this process. Many drugs with diverse properties can inhibit experimental atherosclerosis. These drugs appear to reduce intracellular calcium. The calcium-channel blockers nifedipine, diltiazem and verapamil, which decrease intracellular calcium, also protect animals from experimental atherosclerosis. The relevance of these animal models to human atherosclerosis is uncertain, and there are very few studies concerning regression of atherosclerosis by interfering with calcium fluxes. Further studies will be needed to clarify these points.

Animals↗

PubMed1985

Effects of ryanodine on cat papillary muscle and isolated rat heart.

The neutral alkaloid, ryanodine, has several actions on cardiac muscle. To delineate better its mode of action, we studied ryanodine's effect upon contracting cat papillary muscles under changing loading conditions and stimulation frequencies. We also studied ryanodine's physiologic and metabolic effects upon isolated rat hearts. The results of our study suggest the following: (1) ryanodine causes both decreased release and decreased uptake of calcium by the sarcoplasmic reticulum; (2) elevation of high-energy phosphates secondary to decreased energy requirements is due to decreased calcium availability to the myofilaments during systole; (3) the slowed or incomplete relaxation caused by ryanodine may be a stimulus for myosin phosphorylation; (4) ryanodine probably decreases calcium movement through the sarcolemma and so increases adenosine and inorganic phosphate and decreased cyclic adenosine monophosphate (AMP) concentration in the myocardium; and (5) the effect of ryanodine on altered loading conditions and contraction velocities can be understood in terms of decreased calcium availability to the myofilaments.

Adenosine Triphosphate↗

PubMed1985

Effects of intravenous administration of a new nonionic dimeric contrast medium on the coronary circulation. Comparison with monomeric ionic and nonionic media.

Contrast media injected into the circulation produce a variety of cardiovascular effects. Agents with low osmolality and low concentrations of cations cause considerably less hemodynamic effects. This study compared the effects of a nonionic dimer, iotrol, which has an osmolality (340 mosm/kg) close to that of serum (290 mosm/kg), with a standard ionic monomer, meglumine diatrizoate, and a nonionic monomer, iosimide. The effects of intravenous bolus injection of these three contrast agents on coronary and systemic hemodynamics were studied in eight anesthetized dogs. The influence of the contrast media on subendocardial and subepicardial perfusion was assessed by injecting radioactive microspheres into the left atrium 30 seconds after injection of the media. Alterations in coronary hemodynamics occurred with both iosimide and meglumine diatrizoate. Iotrol produced minimal changes in coronary hemodynamics. Thus, iotrol is the least perturbing contrast indicator and seems the best for use in quantitative digital subtraction and dynamic computed tomography studies designed to measure myocardial perfusion.

Animals↗

PubMed1985

Dynamic CT scanning of the normal canine liver: interpretation of time density curves resulting from an intravenous bolus injection of contrast material.

Seven adult male mongrel dogs were monitored by electromagnetic flow probes and string occluders around the hepatic artery and portal vein. Then, time density curves of the liver, aorta and portal vein were recorded using dynamic CT scanning following the bolus injection of contrast material into a peripheral vein (n = 7) and a mesenteric vein branch (n = 5). Information on total hepatic blood flow could not be obtained from the mesenteric vein injection. The hepatic time density curve could, however, be broken into its two components, hepatic arterial and portal venous flow contribution, by selective ligation of the hepatic artery or portal vein. It could be demonstrated that the arterial component of liver enhancement reached its peak at the end of the aortic wash-out of contrast material. Thus, the hepatic time-density curve could be broken in its two components by superimposing the aortic time density curve onto the hepatic curve. An attempt was made to estimate relative portal venous blood flow by using the slopes or the peaks of both components of the hepatic curve. Using the slopes of the hepatic curve resulted in a consistent underestimation of portal venous blood flow, whereas the peaks gave an estimate of portal venous flow with an accuracy within +/- 8%.

Animals↗