Cardiovascular applications of multi-gate pulsed Doppler systems.
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Biomedical subjects
Publications and source records attributed to R S Reneman.
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Changes in distensibility and cross-sectional compliance of the common carotid artery with age were studied in 80 presumed healthy volunteers, varying in age between 20 and 69 y. The distensibility was assessed from the relative increase in arterial diameter during systole normalized with respect to the arterial pulse pressure. The cross-sectional compliance was obtained by multiplying the distensibility by the arterial diameter. The relative diameter changes of the common carotid artery during the cardiac cycle were recorded on-line with a high resolution multigate pulsed Doppler system. The arterial diameter was assessed from the width of the velocity profiles which can also be recorded on-line with this system. Arterial pulse pressure was determined from brachial artery cuff blood pressure measurements. Both distensibility and cross-sectional compliance of the common carotid artery decreased linearly with age, starting in the third age decade. The reduction in the latter parameter was less pronounced, probably as a consequence of an increase in arterial diameter with age.
Isolated working hearts of 16 month old spontaneously hypertensive rats (SHR, n = 8) and age matched Wistar-Kyoto (WKY, n = 8) rats were exposed to 30 min global normothermic ischaemia followed by 60 min reperfusion. The hearts were routinely perfused at an afterload level of 13.3 kPa and a preload level of 1.0 kPa. The control values of left ventricular pressure, its maximal positive first derivative (dP1v/dtmax), coronary flow per gram heart tissue, and release of lactate and enzymes such as lactate dehydrogenase and aspartate aminotransferase were comparable in both groups. WKY rat hearts ejected almost twice as much perfusate per gram heart weight as the SHR hearts. In pressure-flow curves, obtained during the control period in SHR hearts, cardiac output was independent of changes in afterload, varying between 10.7 and 18.7 kPa. In contrast, in WKY rat hearts increases in afterload resulted in a progressive decrease in cardiac output. Reperfusion of the SHR hearts after 30 min of global normothermic ischaemia resulted in a poor recovery of cardiac output (13% of the control values) and dP1v/dtmax (32%) compared with the values in the WKY rat hearts (66% and 91% of the control values respectively). Reactive hyperaemia was prominent in the WKY rat hearts but completely absent in the SHR hearts. During one hour reperfusion, SHR hearts lost 3.5 times more lactate dehydrogenase and 2.5 times more aspartate aminotransferase than the WKY rat hearts. Pressure-flow curves, obtained during the reperfusion period, showed modest recovery of myocardial function of the WKY rat hearts at the lowest afterload level tested but completely depressed myocardial function of the SHR hearts at all afterload levels. Heart tissue contents of adenosine triphosphate and creatine phosphate after one hour of reperfusion were lower in the SHR than in the WKY rats, but compared with native values a comparable percentage decrease was seen in both groups of rats.
Blood flow, metabolism, and fiber shortening in various layers of left ventricular wall were studied during the initial 5 min of ischemia. In open-chest dogs (n = 51) ischemia was induced by coronary arterial stenosis (median value of mean perfusion pressure distal to stenosis 3.3 kPa). Epicardial deformation measurements with an inductive technique allowed estimation of fiber shortening in inner (eendo,est) and outer layers (eepi) of left ventricular free wall during the ejection phase. The decrease of eendo,est occurred within a few seconds after onset of stenosis, whereas eepi started to decrease 30 s later. After 1 min, eendo,est diminished to zero concomitantly with a reduction of blood flow and creatine phosphate content in the inner layers by 68 and 46%, respectively. In contrast a 60% reduction of eepi was associated with a decrease in blood flow of only 32% and no significant decrease in creatine phosphate in the outer layers. H+ and inorganic phosphate were released simultaneously into the local venous blood starting within 1 min of ischemia. During the initial 5 min of ischemia the content of ATP and glycogen remained unchanged across the ischemic wall. Present results indicate that the decrease of fiber shortening in the inner layers is associated with severe metabolic dearrangements, as reflected by the depletion of creatine phosphate. They also indicate that, during coronary arterial stenosis, impaired fiber shortening in the outer layers may result from the impairment of mechanical function in the inner layers, rather than from metabolic disturbances in the outer layers themselves.
Virtually all fields of physiological research now encompass various aspects of solute transport by convection, diffusion, and permeation across membranes. Accordingly, this set of terms, symbols, definitions, and units is proposed as a means of clear communication among workers in the physiological, engineering, and physical sciences. The goal is to provide a setting for quantitative descriptions of physiological transport phenomena.
The changes induced by continuous aortic cross-clamping in combination with multidose ice-cold St. Thomas Hospital cardioplegia (myocardial temperature below 16 degrees C), or intermittent aortic cross-clamping at 34 or 25 degrees C were evaluated in a randomized study on 72 patients undergoing extensive aorto-coronary bypass surgery. The cumulative release of heart-specific enzymes was very small and no marked ultrastructural changes in mitochondria of both the subepi- and the subendocardial layer of the left ventricular free wall occurred. No differences between the three operation techniques could be observed on the basis of the above-mentioned parameters. Myocardial ATP and glycogen contents were decreased in post-ischaemic tissue in both the normothermic and hypothermic intermittent aortic cross-clamp groups. This decrease was associated with a release of lactate and inorganic phosphate during the repetitive periods of reperfusion. No change in myocardial ATP and glycogen content could be observed in the cardioplegia-treated hearts. St. Thomas Hospital cardioplegia is obviously most effective in preventing changes in myocardial metabolism such as reduction of ATP and carbohydrate stores during the reversible phase of ischaemic insult.
Velocity profiles were determined in rabbit mesenteric arterioles (diameter 17-32 micron). A good spatial resolution was obtained by using the blood platelets as small and natural markers of flow, providing for the first time in vivo detailed, quantitative information about the shape of the velocity profiles in microvessels. In some experiments red blood cell velocity profiles were recorded as well. Easy detection of the cells of interest could be achieved by labelling them selectively with a fluorescent dye and visualizing them by intravital fluorescence video microscopy, using flashed illumination. Pairs of flashes were given with a short, preset time interval between both flashes, yielding in one TV picture two images of the same cell displaced over a certain distance for the given time interval. Velocity and mean radial position of cells, flowing within an optical section around the median plane of the vessel, were determined. The shape of the velocity profiles of platelets and red blood cells was similar. The profiles were flattened as compared to a parabola, both in systole and diastole. Vessel diameter did not change measurably during the cardiac cycle. As an index of the degree of blunting of the profiles, the ratio of the maximal and mean velocity of the profile was used, which is 2 for a parabola and 1 for complete plug flow. The index ranged from 1.39 to 1.54 (median 1.50), and increased with vessel diameter. Calculations showed that the blunting of the profiles cannot be explained by an influence of the finite depth of the optical section.
Four time-domain oriented, real-time frequency estimators, based on the detection of phase, zero-crossings, instantaneous frequency or autocorrelation, were simulated on a digital computer and subjected to computer generated Doppler signals, enabling the investigation of the influence of spectral shape, filtering, frequency shift, noise and quantitation. Three estimators, the autocorrelator as well as the instantaneous frequency detector and the autocorrelator, both with extended frequency range, appeared to be very accurate. They exhibit a bias in the estimator output of less than 2 percent over a wide frequency range, the former up to nearly the Nyquist frequency, the latter two beyond, even for skew spectra and under poor signal conditions regarding bandwidth and noise.
Postoperative hypertension following coronary artery bypass grafting is usually treated with vasodilating agents like nitroprusside. In recent studies ketanserin, a 5-hydroxytryptamine type 2 antagonist, appeared to be effective in the treatment of this clinical syndrome. In 20 patients, divided into two comparable groups, nitroprusside and ketanserin were compared with respect to their haemodynamic and ventilatory profiles. The study showed that both agents were equally effective in decreasing the raised systolic blood pressure, but that ketanserin was more advantageous with respect to the absence of reflex tachycardia and the unchanged shunt fraction.
Cessation of muscle capillary flow was studied in rabbit tenuissimus muscle, using intravital microscopy. Perfusion pressure was reduced by arterial occlusion or simultaneously elevated venous and tissue pressure. Muscle capillary flow ceased in the presence of arteriolar dilation at a median perfusion pressure of 17.5 mmHg during arterial occlusion and at 25.3 mmHg in case of simultaneously increased tissue and venous pressure. The pressure difference of 7.8 mmHg was confirmed in a series of experiments where arterial occlusion and increased tissue pressure were randomly alternated in the same animal. The mechanisms responsible for the difference in pressure level at which flow ceases in the capillaries under these circumstances are incompletely understood. Possible mechanisms are discussed.
The intradermal injection in rat skin of washed, thrombin-activated platelets produces an increase in vascular permeability, the intensity of which increments with the platelet concentration. Pretreatment of the recipient animals with serotonergic antagonists, including the specific 5-HT2 receptor blocker ketanserin, potently inhibits the platelet-mediated and the 5-HT-induced vascular defect. Amine depletion of platelets or skin tissues with reserpine reduces the response to platelets. Platelet prostanoid and lipoxygenase derivatives play no major role in the vascular response to platelet. The permeability increase induced by exogenous 5-HT and by activated platelets is reduced by alpha 1-adrenergic stimulation with noradrenaline or phenylephrine and by beta 2-stimulation with terbutaline or isoprenaline, and is potentiated by adenosine; this points to a modulation of permeability by blood flow changes and to a direct beta-adrenergic effect at the endothelial cell membrane. This study demonstrates a predominant role for 5-HT in the platelet-mediated vascular permeability increase in a sensitive species like the rat.
Oliver and coworkers hypothesized that under certain circumstances NEFA (non-esterified fatty acids = FFA = free fatty acids) might be toxic for myocardial function. Unambiguous conclusions on the putative detrimental effect of intracellularly localized NEFA are hampered by contradictory values published for the NEFA content in normoxic myocardial tissue. From studies in which the assay procedures were carefully evaluated, one might conclude that the NEFA content in dog and rat myocardial tissue will not exceed 60 and 150 nmol/g wet weight, respectively. However, recently Victor and coworkers found considerably higher NEFA values in rat myocardial tissue and suggested that the low NEFA values as measured, for example, in our laboratory, resulted from incomplete extraction when the Folch medium was applied instead of the Dole mixture. Since Victor and coworkers used a modified Dole procedure as described by Hagenfeldt, we evaluated the Folch procedure as well as the original Dole technique and the modified version. Our findings indicate that the lower values found by the Folch technique are more likely to be correct. Incomplete extraction of NEFA did not occur, whereas hydrolysis and transmethylation of phospholipid fatty acids were observed in case of the (modified) Dole procedures.
The dynamic capacitance of epicardial coronary arteries (i.d. greater than or equal to 0.4 mm) in vivo was assessed from the volume stiffness and volume of these arteries. The volume stiffness was derived from the pressure wave front velocity as determined in dogs by measuring the delay time between the pressure pulses recorded proximal and distal to a segment of the anterior descending branch of the left coronary artery. The pressure pulse was generated elsewhere in the arterial system during diastole. The volume of the epicardial coronary arteries was calculated from the lengths and diameters as measured in araldite casts, making corrections for in-vitro/in-vivo differences in dimensions. The dynamic capacitance of the right coronary artery, and the anterior descending and circumflex branches of the left coronary artery at an arterial pressure of 13.3 kPa and a frequency between 7 and 30 Hz was found to be 0.0024 +/- 0.0013, 0.0062 +/- 0.0028 and 0.0079 +/- 0.0035 mL/kPa (mean +/- SD), respectively. The total capacitance of the epicardial coronary arteries was calculated to be (0.007 mL/kPa)/100 g, which is small as compared to the total capacitance of the coronary vasculature, including the intramyocardial compartment, which is in the order of (0.5 mL/kPa)/100 g [1].
In our concept of the interaction between intramyocardial pressure (IMP) and myocardial perfusion, IMP is defined as the hydrostatic pressure in the soft tissue surrounding the myocardial fibers. In a mathematical model of the mechanics of the left ventricle the latter definition results in values for IMP equal to left ventricular pressure in the inner layers of the wall, and a continuous decrease across the wall to zero in the outer layers. Modulation of coronary artery flow during the cardiac cycle is predominantly due to compression of the coronary vasculature by the IMP during the systolic phase of the cardiac cycle, resulting in back-squeezing components of this flow. In a mathematical model of the dynamics of the coronary circulation, containing a large capacitance at the level of the coronary microvasculature, the modulations of coronary artery flow were found to be similar to those found in animal experiments in open-chest dogs.
The distribution of blood platelets flowing in arterioles (21-35 microns) of the mesentery of anesthetized rabbits was studied using intravital fluorescence microscopy. Sites were selected without upstream branch points within at least 10 vessel diameters. The distribution was determined by counting in flashed video frames the number of platelets present in each of six equal segments across the vessel. Only platelets were counted that could be localized objectively within a thin optical section around the median plane of the vessel. It could be shown that differences in counting volume between the six segments were negligible. Because of the use of flashed pictures (flash duration less than 0.1 ms; interval 180 ms), the method is independent of differences in velocity over the cross-sectional area of the vessel. In all measurements (15 sites in 13 vessels in 10 animals) the distribution was nonuniform, the wall segments containing the highest platelet numbers. The general distribution as calculated from all measurements (total platelet number 6,571) and expressed in percentages was found to be 23.0, 14.6, 12.5, 12.1, 13.6, and 24.2.
Multiple indicator-dilution experiments were done to compare the transcapillary exchange of tracer amounts of L-[14C]ascorbate and D-[3H]glucose (against an intravascular reference 131I-albumin) in Ringer-perfused (5 mM glucose) isolated rabbit hearts. The indicator-dilution curves for the two were virtually superimposed over the first 40-80 s. Estimates of the capillary permeability-surface area products, PSc, were the same, 2.3 +/- 0.7 (SD) ml X g-1 X min-1 (n = 18), in accord with the coincidence of their instantaneous extractions. The similarity of glucose and ascorbate permeabilities is explained by the similarity in molecular weights and passive diffusivity, their lipophobic nature, and the paucity of carrier-mediated endothelial transport for either molecule. The data were analyzed via a model composed of aggregates of spatially distributed capillary-tissue units (capillary blood, interstitium, myocytes) accounting for the heterogeneity of regional flows. The interstitial volumes in this preparation are enlarged, 0.30 +/- 0.04 ml/g. There is substantial entry into myocardial cells, the cell permeability-surface area products being approximately 2-3 ml X g-1 X min-1 for ascorbate and glucose. The estimated volumes of interstitial and intracellular space, 0.30 and 0.47 ml X g-1 X min-1, reflect interstitial edema and are very close to measured values, giving reassurance concerning the methods of modeling analysis.
To study the myocardial washout of ascorbate, the applicability of polarographic detection of ascorbate ions by a platinum electrode (sensitive area 0.03 mm2) was investigated, in both a calibration setup (sampling flow along the electrode: 100 microliter X s-1) and isolated, retrogradely perfused rabbit hearts. In the calibration setup at pH 7.4, the sensitivity of the electrode was 70 microA/mol. This sensitivity increased moderately with increasing pH (13%/unit pH) and increasing sampling flow rate (14% at an increase from 100 to 150 microliter X s-1). In the isolated hearts, ascorbate infused into the aorta was detected in a right ventricular drain by the electrode as well as by the use of 14C-labeled ascorbate. Both recorded time courses were similar except for a scaling factor dependent on flow velocity. During continuous infusion the arteriovenous difference of ascorbate was 2 +/- 2% (SD), indicating a relatively low consumption of ascorbate by the isolated heart. We conclude that polarographic measurement of ascorbate in the coronary effluent of an isolated rabbit heart can be performed on-line and relatively easily.
Velocity patterns in and distensibility of the carotid artery bulb were studied in younger (20 to 30 years; n = 11) and older (50 to 60 years; n = 9) volunteers without detectable lesions of the cervical carotid arteries by means of a high-resolution, multigate, pulsed Doppler system coupled to a B mode imager. In the bulb the axial velocities were highest on the side of the flow divider, while regions of flow separation and recirculation were observed on the side opposite to this divider. Flow separation and recirculation were less pronounced and less common in the older subjects. Flow separation was not continuously present throughout the cardiac cycle. The distensibility of the carotid arteries was significantly diminished in older subjects, especially in the bulb. The velocity patterns in the carotid artery bulb of younger subjects corroborate the patterns observed in models. The diminished flow separation and recirculation in the older subjects might result from alterations in distensibility at the transition from common to internal carotid artery with increasing age.