Ischemia-induced arachidonic acid accumulation and prostanoid release during reperfusion in the isolated rat heart.
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6-Ketoprostaglandin F1 alpha↗
Biomedical subjects
R S Reneman
Publications and source records attributed to R S Reneman.
Cardiovascular effects of dl-nebivolol and its enantiomers--a comparison with those of atenolol.
In the present study, we investigated the cardiovascular effects of dl-nebivolol, a newly synthetized, chemically novel, beta 1-adrenoceptor antagonist and its enantiomers, d-nebivolol (SRRR) and l-nebivolol (RSSS), in closed-chest anesthetized dogs, using atenolol as a reference substance. Results from preliminary studies in vitro indicate that d-nebivolol is the beta 1-adrenoceptor antagonist and that l-nebivolol is practically devoid of beta-adrenoceptor-blocking properties. Unlike atenolol, dl-nebivolol does not depress left ventricular function and slightly, but significantly, reduces peripheral vascular resistance over the dose range from 0.0025 to 0.04 mg.kg-1 i.v. These observations are likely to be clinically relevant because one daily oral dose of 5 mg dl-nebivolol effectively lowers arterial blood pressure in patients with hypertension. The favorable hemodynamic profile of dl-nebivolol can be ascribed to the l-enantiomer because the cardiovascular effects of this enantiomer are similar to those of the racemate. The cardiovascular profile of the d-enantiomer is similar to that of atenolol, albeit that its depressant effect on left ventricular function occurs at higher doses.
Animals↗
Release of fatty acid-binding protein from isolated rat heart subjected to ischemia and reperfusion or to the calcium paradox.
The release of cardiac fatty acid-binding protein (cFABP) and of fatty acids from isolated rat hearts was measured during both reperfusion following 60 min of ischemia and the calcium paradox (readmission of Ca2+ after a period of Ca2+-free perfusion). Total cFABP release was much more pronounced after Ca2+ readmission (over 50% of tissue content) than during post-ischemic reperfusion (on average, 3% of tissue content), but in both cases, it closely paralleled the release of lactate dehydrogenase. Only minor amounts of long-chain fatty acids, if any, were released from the heart. These observations are challenging the idea that cFABP plays a fatty acid-buffering role under the pathophysiological conditions studied.
Animals↗
Determination of prostaglandins and thromboxane in whole blood by high-performance liquid chromatography with fluorimetric detection.
A highly sensitive and specific assay for the quantitation of prostaglandins (PGs) such as PGE1, PGE2, PGF1 alpha, PGF2 alpha, 6-keto-PGF1 alpha, and including thromboxane B2, is described. The method involves the addition of PGF1 alpha and PGE1 as the internal standards, extraction from whole blood and purification by silica gel column chromatography. Following conversion into the methoximes, purification by reversed-phase chromatography and esterification with panacyl bromide, samples are analysed by high-performance liquid chromatography with fluorimetric detection. The lower limit of detection of the eicosanoids 6-keto-PGF1 alpha, thromboxane B2 and PGF2 alpha in blood is ca. 50 pg/ml and that of PGE2 is 100 pg/ml. Assay linearity is demonstrated over a range from 60 pg to 60 ng of eicosanoid injected. The method allows simultaneous assessment of prostaglandins and thromboxane extracted from complex biological fluids at picogram levels.
Chromatography, High Pressure Liquid↗
Thromboembolic reaction following wall puncture in arterioles and venules of the rabbit mesentery.
The walls of rabbit mesenteric arterioles and venules (diameter 20 to 40 microns) were punctured with glass micropipets (tip diameter 6 to 8 microns). Thromboembolic reactions resulting from this standardized, small mechanical vessel wall injury could be quantified in vivo with the use of intravital video-microscopy. Following induction of the injury thrombus growth started immediately (less than 0.1 s). Bleeding times were short, on the average less than 2 s, and did not differ between arterioles and venules. The duration of the embolization process was significantly longer in arterioles than in venules (median 101 and 17 s, respectively), and more emboli were produced in arterioles than in venules (median 6 and 1, respectively). Arteriolar thrombi were more effective in plugging the punctured holes than venular thrombi. The differences in thromboembolic reaction between arterioles and venules, as found in the present study, can probably not be explained by fluid dynamic factors.
Animals↗
Effects of pyruvate on post-ischemic myocardial recovery at various workloads.
In the present study the hemodynamic and metabolic effects of pyruvate (5 mM), added as cosubstrate to glucose (11 mM) perfused, transiently ischemic, isolated working rat hearts, were evaluated. During 2 h of normoxic perfusion pyruvate improved functional stability, prevented depletion of glycogen and triacylglycerol stores, and increased non-esterified fatty acid (NEFA) levels, even at relatively high workloads. The elevated NEFA levels are in line with the notion that pyruvate competes with endogenously produced fatty acids for oxidative energy production. After 45 min of global ischemia pyruvate was found (a) to affect markedly the relative contribution of ATP, ADP and AMP to the total adenine nucleotide content and (b) to stimulate the degradation of glycogen and to enhance the accumulation of lactate, suggesting enhanced anaerobic ATP production. After restoration of flow pyruvate reduced the incidence of fibrillation and markedly improved recovery of cardiac output at both normal and high workload. Pyruvate did neither attenuate the release of lactate dehydrogenase, a marker for cell death, nor improve the conservation of the total adenine nucleotide and ATP content of hearts reperfused for 30 min. The latter findings indicate that hemodynamic recovery during reperfusion in the presence of pyruvate is neither related to the absolute tissue content of ATP nor to a reduction of irreversible cell damage, and suggest that pyruvate exerts its advantageous hemodynamic effects rather by improving the condition of reversibly damaged cells during reperfusion.
Animals↗
Deformation of the dog aortic valve ring during the cardiac cycle.
Changes in strain in the line of aortic valve leaflet attachment (aortic ring) were measured during the cardiac cycle by means of an inductive technique. To that purpose coils were sutured to each commissure and base point of the aortic ring, when the animals were on a cardiopulmonary bypass. After bypass and stabilization of the hemodynamic variables changes in the aortic strain were measured at aortic pressures ranging from 4 to 20 kPa. Aortic pressure at the level of the commissure points and left ventricular pressure were measured to assess transvalvular pressure. Commissure strain appeared to depend on aortic and transvalvular pressure throughout the cardiac cycle. At an aortic pressure of 10 kPa (75 mm Hg), the derivative of commissure strain to aortic pressure was found to be 1.9 x 10(-5) +/- 1.2 x 10(-5) Pa-1 (mean +/- SD). During the ventricular ejection phase commissure strain was 0.04 +/- 0.03 higher than during ventricular filling. Maximum variations in basal strain during the cardiac cycle ranged from 0.03 to 0.15. During the ejection phase the basal segments adjoining the myocardium shortened whereas the segment close to the non-contracting anterior mitral valve leaflet lengthened. Strain between a base and a commissure point of the aortic ring were synchronous with the cardiac cycle, but no specific pattern could be found.
Animals↗
Multichannel storage and display system to record the electrical activity of the heart.
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Data Collection↗
An experimental analysis of the flow field in a three-dimensional model of the human carotid artery bifurcation.
Steady flow measurements were carried out in a rigid three-dimensional model of the human carotid artery bifurcation at a Reynolds number of 640 and a flow division ratio of 50/50. Both axial and secondary velocities were measured with a laser-Doppler anemometer. In the bulb opposite to the flow divider a zone with negative axial velocities was found with a maximal diameter of about 60% of the local diameter of the branch and a cross-sectional extent of about 25% of the local cross-sectional area. In the bulb the maximum axial velocity shifted towards the divider wall and at the end of the bulb an axial velocity plateau arose near the non-divider wall. Halfway through the bulb, secondary flow showed a vortex through which fluid flowed towards the divider wall near the bifurcation plane and back towards the non-divider wall near the upper walls.
Blood Flow Velocity↗
The diagnosis of minor to moderate atherosclerotic lesions in the carotid artery bifurcation by means of spectral broadening combined with the direct detection of flow disturbances using a multi-gate pulsed Doppler system.
The diagnostic accuracy of noninvasive detection of carotid artery lesions with a diameter of less than 50% (minor to moderate) and greater than 50% reduction (severe) with the use of a multi-gate pulsed Doppler system (spectral analysis combined with the detection of flow disturbances) was studied in patients with focal neurological symptoms. Biplane arteriography was used as a reference. For all lesions the diagnostic accuracy (observed agreement), sensitivity and specificity was 88, 92, and 84%, respectively, and 84, 83, and 84%, respectively, when only minor to moderate lesions were considered. Kappa, a chance-corrected measure of agreement, which takes into account the marginal distribution of the data and, hence, may be considered to be a better parameter to describe diagnostic accuracy, was found to be 82.2%. The results in this study compare favorably with those obtained in studies employing duplex techniques (B-mode image combined with single-gate pulsed Doppler) and indicate that minor to moderate carotid artery lesions are detected rather accurately with the use of a multi-gate pulsed Doppler system.
Arteriosclerosis↗
Carotid artery wall properties in normotensive and borderline hypertensive subjects of various ages.
The vessel wall properties of the common carotid artery were studied noninvasively in normotensive and borderline hypertensive male volunteers of various ages with the use of a multi-gate pulsed Doppler system. In the younger age group (20-35 y) both distensibility and cross-sectional compliance were significantly less in the borderline hypertensive group. In the older borderline hypertensive subjects (50-69 y) distensibility (p less than 0.05) and cross-sectional compliance (p = 0.06) were also less than in the control subjects. The reduced distensibility and cross-sectional compliance likely result from a decrease in arterial wall elasticity because the relative increase in common carotid artery diameter during systole is diminished in borderline hypertensives, despite the fact that their pulse pressure is similar to or higher than that in control subjects. The less pronounced differences in vessel wall properties between borderline hypertensive and normotensive volunteers in the older age group may be a consequence of the changes in these properties with age, partly masking the alterations due to borderline hypertension. Since the stiffer behavior of the common carotid artery in borderline hypertensives is associated with relatively slight changes in blood pressure, the question can be raised whether the alterations in arterial wall properties are really a result of the elevated arterial blood pressure; these alterations might develop independent of the blood pressure elevation.
Adult↗
Differences in carotid artery wall properties between presumed-healthy men and women.
The vessel wall properties of the common carotid artery were noninvasively studied in 109 normotensive, presumed normal male and female volunteers of various ages (20-69 y) with the use of a multi-gate pulsed Doppler system. This system allows the on-line recording of velocity profiles and the relative changes in carotid artery diameter during the cardiac cycle (delta d/d). From the width of these profiles the systolic internal diameter (d) of the carotid artery can be determined. With the use of d, the maximal increase in delta d/d during systole and the pulse pressure, as measured in the brachial artery (delta p), the distensibility coefficient and the cross-sectional compliance were calculated. Both distensibility and cross-sectional compliance were significantly lower in females than in males, irrespective of age. This likely results from a stiffer arterial wall behavior in females, because the relative increase in vessel diameter during the cardiac cycle is lower in females than in males, despite the fact that their pulse pressure values are not significantly different. The carotid artery diameters were similar in men and women. The findings in the present study indicate that the common carotid artery is stiffer in females than in males of comparable age. Therefore, sex-dependent differences have to be considered in the interpretation of arterial distensibility and cross-sectional compliance.
Adult↗
Automated calculation of stenosis diameters from the width of the velocity jet with the use of a multi-gate pulsed Doppler system.
The aim of this study was to evaluate an algorithm for automated estimation of the width of a jet stream originating from a stenosis. The evaluation was performed in a pulsatile flow model. The width of the jetstream was assessed by measuring the diameter of the region with relatively high velocities (the jet) in the velocity profiles, as recorded with a multi-gate pulsed Doppler system. Measurements were performed at 3, 6, and 9 mm downstream of three different stenoses (stenosis diameter: 3, 5, or 8 mm) at different Reynolds numbers (200-1600) based on time averaged flow velocity for a tube of diameter 15 mm. The developed algorithm was used successfully for automated detection and quantification of jet flow diameters downstream to a stenosis. The algorithm can be used for calculating the stenosis diameter notwithstanding a theoretically predictable overestimation of about 1 mm, depending on the Reynolds number and the distance from the stenosis.
Algorithms↗
The myocardial content of fatty acids and phospholipids during the calcium paradox.
Readmission of Ca2+ after a short period of Ca2+-free perfusion results in a rapid and massive release of cytoplasmic proteins from the heart (calcium paradox). Maximal release rates of proteins are already reached within 2 min after Ca2+ repletion. The precise mechanism underlying the loss of cellular membrane integrity, resulting in the loss of intracellular proteins, has not been clearly defined. The present study indicates that neither substantial degradation of phospholipids, being important constituents of myocardial membranes, nor accumulation of fatty acids occur during the early phase (within 1.5 min) of Ca2+ readmission. Thereafter significant amounts of such fatty acids as arachidonic acid accumulate in the Ca2+ repleted hearts. The late onset of arachidonic acid accumulation, most likely reflecting phospholipid degradation, is considered to be an epiphenomenon occurring in myocardial cells which became heavily damaged, as indicated by the substantial loss of lactate dehydrogenase, during the early phase of Ca2+ repletion. Interestingly, tissue fatty acid levels increased already significantly during the Ca2+-free perfusion period (by about 240%). The significance of this finding is not completely understood. A possible causal relationship with disturbed ion homeostasis during the induction of calcium paradox remains to be established.
Animals↗
Epidural spinal cord electrical stimulation improves microvascular blood flow in severe limb ischemia.
Epidural spinal cord electrical stimulation (ESES) was performed on 10 patients with severe limb ischemia due to atherosclerotic disease. Microcirculatory parameters were assessed before and after ESES. Bright field microscopy was used to assess capillary diameters and red blood cell (RBC) velocity in the dorsum of the foot. Fluorescein microscopy was used with intravenously injected sodium fluorescein to study capillary density and sodium fluorescein appearance time in the dorsum of the toe. The systolic ankle/arm pressure ratio and toe pressure measurements were used as macrocirculatory parameters. After ESES, clinical improvement was confirmed by intravital microscopy. Capillary density increased (p less than 0.001), RBC velocity in capillaries already perfused before ESES increased from 0.054 mm/sec to 0.762 mm/sec (p less than 0.001), and sodium fluorescein appearance time decreased from 72 to 45 seconds (p less than 0.001). Capillary diameter did not change significantly so that the increase in RBC velocity may be interpreted as enhanced volume flow. Systolic ankle/arm pressure ratios and digital arterial pressure did not change significantly. The current results show that in patients with severe occlusive arterial disease of the lower limbs, ESES recruits capillaries not perfused in the control situation and enhances skin blood flow, improvements that may explain the beneficial clinical effects of ESES.
Aged↗
Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist.
The pharmacological profile of nebivolol (N), a chemically novel beta-adrenergic antagonist, was assessed in investigations on isolated tissues, awake spontaneously hypertensive rats (SHR), closed-chest anesthetized dogs, and humans. In vitro, N was found to be a potent antagonist of beta 1-adrenergic receptors (A2 value, 5.8 X 10(-9) M) and only a weak beta 2-adrenergic antagonist (A2 value, 1.7 X 10(-6) M). The selectivity for the beta 1-adrenergic receptor was higher for N than for any of the reference compounds. In dogs--similarly with atenolol--N was more potent in blocking the isoprenaline (I)-induced increases in left ventricular performance than the I-induced decrease in arterial pressure. In dogs, as compared with propranolol, N (0.025 and 0.01 mg.kg-1 i.v.) increased cardiac output and stroke volume, lowered systemic vascular resistance, and had no significant effect on the variables related to left ventricular contraction. In contrast to other beta-adrenergic antagonists, N acutely lowered arterial blood pressure in SHR (1.25 mg.kg-1 i.p.) and in hypertensive patients (1 oral dose of 5 mg) for several hours. In healthy volunteers N (5 mg) lowered systemic vascular resistance during daily oral treatment and did not negatively affect left ventricular function. In conclusion, N is a potent and selective beta 1-adrenergic blocking agent with an interesting hemodynamic profile. In hypertensive subjects and SHR, a single dose lowers arterial blood pressure for substantial periods of time.
Adrenergic alpha-Antagonists↗
On-line measurement of aortic valve ring deformation during the cardiac cycle.
An electronic device is described for the measurement of relative changes in segment length within the aortic valve ring during the cardiac cycle. The technique is based on the principle of magnetic induction. A magnetic field generated in one coil induces a voltage in another coil. From the amplitude of this voltage the strain between both coils can be determined because the strength of the magnetic field decreases with distance. In vitro, over a range of 5-25 mm, strains less than or equal to 0.20 strain units can be measured with an accuracy of 0.008 strain units. The frequency response is 0-150 Hz (-3 dB). By varying the generator and receiver assignment at a frequency of 2 kHz and multiplexing the signals of six coils, six strains can be measured simultaneously. As an example, simultaneous recordings of commissure strains in the aortic valve and left ventricular and ascending aortic pressures, as obtained in open-chest dogs, are shown.
Animals↗
Wall shear rate in arterioles in vivo: least estimates from platelet velocity profiles.
Velocity profiles, as determined in vivo in rabbit mesenteric arterioles with fluorescently labeled platelets as natural flow markers, were used to calculate least estimates of the actual wall shear rate in these microvessels (17-32 micron diam). The fit of the velocity data points described the profile as close to the wall as 0.5 micron. To satisfy the no-slip condition, a thin layer of fluid with a steep velocity gradient near the wall was assumed. Least estimates of wall shear rate, as calculated from the fitted platelet-velocity profiles and using the mean velocity gradient in this layer of fluid, ranged from 472 to 4,712 s-1 with a median value of 1,700 s-1. Red blood cell center-line velocities varied between 1.3 and 14.4 mm/s (median 3.4). The wall shear rates were at least 1.46-3.94 (median 2.12) times higher than expected on the basis of a parabolic velocity distribution but with the same volume flow in the vessel. Considerable spatial differences in wall shear rate might exist even within a short segment of a vessel.
Animals↗