Local inhomogeneities in wall distensibility in the carotid artery bifurcation in borderline hypertensives.
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Biomedical subjects
Publications and source records attributed to R S Reneman.
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Basically 2 methods are available to transcutaneously assess the compliance of arteries using ultrasound. One method is based on the pulse wave velocity (mean compliance over a segment), while the other is based on the local distension waveform of an artery (local compliance). Both methods assume compliance to be independent of local blood pressure. The latter method requires accurate assessment of the diameter of the artery under investigation at the onset of a cardiac cycle, the distension during the cardiac cycle and the local pulse pressure. A new method is described to obtain reliable estimates for the arterial diameter and the change in diameter as function of time.
Microcirculatory and haemorheological parameters were investigated before and after plasmapheresis in eighteen patients with secondary Raynaud's phenomenon based on progressive systemic sclerosis. After 4 plasmaphereses, once a week, all patients claimed explicit improvement of their complaints. Raynaud's phenomenon and especially the reaction upon cold provocation had disappeared and skin ulcers healed. Red blood cell (RBC) velocity increased significantly (p less than 0.001) after 4 weeks plasmapheresis. RBC aggregation and plasma viscosity were significantly lower (p less than 0.001) after the last plasmapheresis than before treatment. After 3 years four patients were still free of complaints, but in 14 patients the symptoms of Raynaud's phenomenon had reappeared after 6 to 9 months. The skin ulcers, however, did not return in these patients. RBC aggregation and plasma viscosity returned to the initial values after 9 months, while skin capillary blood flow remained significantly enhanced for 24 months. The finding that restoration of RBC aggregation and plasma viscosity to normal level is associated with enhanced skin capillary blood flow, indicates that disturbed haemorheology plays a role in the diminished skin blood flow, as observed in patients with secondary Raynaud's phenomenon. In these patients, plasmapheresis can be considered to treat severe ischemia of the digits.
Atherosclerosis is an important cause of cardiovascular morbidity and mortality. A good arterial compliance has been suggested to protect large vessels from atherosclerosis. Arterial compliance is diminished in patients with essential hypertension. The influence of verapamil (calcium-antagonist) and nebivolol (beta-adrenoceptor antagonist) on the vessel-wall properties of the common carotid artery were investigated. The two drugs improved compliance of the common carotid artery. Results from other studies on arterial compliance and antihypertensive drugs are also discussed.
In this study the effect of l-nebivolol on the blood pressure lowering action of d-nebivolol was investigated after intraperitoneal administration of the drugs to spontaneously hypertensive rats. Doses of l-nebivolol which did not affect blood pressure when given alone potentiated the decrease in systolic and diastolic blood pressure induced by 1.25 mg.kg-1 d-nebivolol. The potentiating effect of l-nebivolol was seen at doses higher than 0.16 mg.kg-1. At 1.25 mg.kg-1 d-nebivolol significantly reduced the heart rate, an effect which was not potentiated by l-nebivolol in doses up to 1.25 mg.kg-1. Higher doses of l-nebivolol (2.5 and 5.0 mg.kg-1) in combination with 1.25 mg.kg-1 d-nebivolol not only lowered the blood pressure further, but also significantly reduced the heart rate; thus at these doses the enantiomers together exerted more pronounced beta 1-adrenoceptor blocking properties. This is probably disadvantageous, because d,l-nebivolol has been shown to decrease arterial blood pressure in hypertensive patients and animals before it reaches its maximal beta 1-adrenoceptor blocking effect. Therefore, the racemic mixture of 50% d-nebivolol and 50% l-nebivolol seems to contain the two compounds in near optimal proportions for an antihypertensive effect.
The influence of changes in pCO2, pH and pO2 on the aggregation of rabbit blood platelets was studied in vitro, with emphasis on hypercapnia, acidosis and hypoxia. Hypercapnia combined with acidosis caused a reduction in rabbit platelet aggregation, as induced by collagen, thrombin and ADP; the effect being most pronounced with collagen and smallest with ADP. Hypoxia reduced thrombin induced platelet aggregation, but had no effect on ADP and collagen induced aggregation. Synergistic activation of rabbit platelets, as induced by the addition of serotonin to platelet rich plasma together with collagen or ADP, seemed to be equally sensitive to changes in pCO2 and pH as activation by the individual agents, and insensitive to changes in pO2.
In this survey the possible role of serotonin in such acute disorders as systemic and pulmonary hypertension following cardiac surgery is discussed. Although platelets are activated during cardiopulmonary bypass, the increase in serotonin plasma levels is limited because the serotonin released is taken up by normal platelets and endothelial cells. This does not imply that serotonin is not involved in the origin of systemic hypertension during and after cardiac surgery, because subthreshold or threshold doses of this amine amplify the vasoconstrictive effect of, for example, epinephrine and norepinephrine, the levels of which are significantly elevated under these circumstances. That serotonin plays a role through its amplifying effect is supported by the finding that ketanserin, a specific S2-serotonergic receptor antagonist with alpha 1-adrenergic receptor blocking properties, effectively lowers arterial blood pressure in patients with systemic postoperative hypertension by combined blockade of these receptors. The compound is also effective in the treatment of pulmonary hypertension after valve replacement, indicating that serotonin plays a role in the origin of this disorder. This idea is supported by the experimental finding that serotonin induces pulmonary hypertension. It is an interesting observation that, unlike such compounds as nitroprusside, ketanserin does not affect intrapulmonary shunting in patients with systemic hypertension and even reduces the intrapulmonary shunt fraction in patients with pulmonary hypertension. These findings indicate that this compound dilates the resistance vessels in well-ventilated, but not in poorly ventilated areas, and may dilate constricted bronchi.(ABSTRACT TRUNCATED AT 250 WORDS)
A finite element approximation of steady flow in a rigid three-dimensional model of the carotid artery bifurcation is presented. A Reynolds number of 640 and a flow division ratio of about 50/50, simulating systolic flow, was used. To limit the CPU- and I/O-times needed for solving the systems of equations, a mesh-generator was developed, which gives full control over the number of elements into which the bifurcation is divided. A mini-supercomputer, based on parallel and vector processing techniques, was used to solve the system of equations. The numerical results of axial and secondary flow compare favorably with those obtained from previously performed laser-Doppler velocity measurements. Also, the influence of the Reynolds number, the flow division ratio, and the bifurcation angle on axial and secondary flow in the carotid sinus were studied in the three-dimensional model. The influence of the interventions is limited to a relatively small variation in the region with reversed axial flow, more or less pronounced C-shaped axial velocity contours, and increasing or decreasing axial velocity maxima.
It is a matter of continuous debate whether mechanical and metabolic activities are differently distributed across the left ventricular wall. It has been suggested that under normal circumstances the subendocardial layers have a higher workload and, hence, higher energy requirements than the subepicardial layers. Direct assessment of the transmural distribution of workload in the left ventricular wall is hampered by technical difficulties. Recent attempts to estimate the transmural heterogeneity in workload by mathematical models indicate that major differences between subendocardial and subepicardial layers are not very likely. Flow determinations with adequately sized microspheres or molecular flow markers indicate that transmural flow distribution is close to unity. The observation in some studies that oxygen pressure and venous hemoglobin oxygen saturation is lower in subendocardial than in subepicardial layers suggests a higher metabolic activity in the former layers. However, other biochemical parameters, such as metabolic fluxes, enzyme activities, or concentrations of substrates, cofactors and high-energy phosphates and related compounds, fail to reveal a consistent and substantial transmural difference in energy metabolism. It cannot be excluded that under certain circumstances energy requirements are unevenly distributed across the left ventricular wall. For example, the size of the heart, the awake or anesthetized state of the animal, the level of overall cardiac workload and the efficiency of metabolic-mechanical conversion might influence to some extent the distribution of energy metabolism across the left ventricular wall. Although at present no definite conclusions can be drawn, it is likely that the transmural differences in energy requirements of normally functioning, intermediate-size hearts are limited. Small differences in the order of 10-20% between the subendocardial and subepicardial layers cannot be excluded.
Abdominal aorta constriction was performed in 10-week-old Lewis rats (Aoband). Ten weeks later the hearts were isolated and attached to a non-recirculating perfusion apparatus. The hearts could eject against a diastolic aortic pressure of either 60 or 100 mmHg. The functional recovery was compared with that of hearts of sham-operated (Sham) rats. After 45 min of global ischemia, Sham hearts regained cardiac output up to 75% and 70% of the pre-ischemic levels at 60 and 100 mmHg, respectively. At 60 mmHg Aoband hearts showed a minor recovery of ejection function. However, at 100 mmHg the recovery of Aoband hearts was completely comparable with that of Sham hearts. At 60 mmHg but not at 100 mmHg, the pre-ischemic and post-ischemic coronary flow was lower in Aoband than in Sham hearts (P less than or equal to 0.05). During the initial reperfusion phase Sham hearts, perfused at 60 mmHg, released more degradation products of adenine nucleotides and lactate dehydrogenase (LDH) than Aoband hearts (P less than or equal to 0.05), while the Aoband hearts lost more degradation products and LDH than the Sham hearts later during the reperfusion phase (P less than or equal to 0.05). In the groups perfused at 60 mmHg, higher tissue levels of ATP were found in Sham than in Aoband hearts at the end of the reperfusion period (P less than or equal to 0.05). However, at 100 mmHg comparable levels were found in the Sham and Aoband hearts. It is concluded that the height of the coronary perfusion pressure is of critical importance for the post-ischemic functional recovery of the compensated hypertrophied heart. At sufficiently high perfusion pressure levels, the functional and biochemical recovery of the hypertrophied heart is at least as good as in the non-hypertrophied heart. However, in the hypertrophied heart a coronary perfusion pressure which is too low leads to relative underperfusion during the initial reperfusion period which is associated with severely depressed cardiac performance and delayed wash-out of metabolites and intracellular enzymes.
In normoxic hearts a limited number of multilamellar vesicles was found in both endothelial cells and myocytes. The total number of multilamellar vesicles observed in myocytes, particularly those extruded from mitochondria, significantly increased in hearts rendered ischemic for at least 60 mins. The number of multilamellar vesicles extruded from sarcolemma was increased in hearts reperfused after this period of ischemia. The number of multilamellar vesicles in or adjacent to lipid droplets was independent of the duration of ischemia. Multilamellar vesicles were similar in size and periodicity of the lamellae. It is proposed that the number of multilamellar vesicles can be used to quantitate ischemic membrane injury. The formation of multilamellar vesicles was significantly related in time to (a) the accumulation of arachidonic acid and total fatty acids; (b) a decrease in the tissue content of ATP and (c) the release of lactate dehydrogenase (LDH). No significant alterations in the total tissue content of triacylglycerols and phospholipids were detected. The amount of arachidonic acid accumulated in the hearts reflects the degradation of only a minor fraction of the phospholipid pool. Assuming a close relationship between phospholipid degradation, induction of multilamellar vesicles and loss of cellular integrity, the present findings might indicate that the loss of a small part of phospholipids might have serious pathophysiological consequences, as indicated by the morphological changes in cellular membranes and the release of cytoplasmic macromolecules.
To assess the nature of ischemia- and reperfusion-induced lipid changes and their consequences for myocardial function and integrity, Krebs-Henseleit perfused, isolated, working rat hearts were treated with nicotinic acid or mepacrine, putative inhibitors of triacylglycerol and phospholipid hydrolysis, respectively. In non-treated hearts 60 min ischemia resulted in a marked rise in myocardial fatty acid (FA) content. The FA content sharply increased further during 30 min reperfusion. Seven out of 16 (44%) hearts fibrillated continuously during reperfusion. Post-ischemic recovery of cardiac output (CO) of the non-fibrillating hearts amounted to 68 +/- 15% of the preischemic value. Nicotinic acid (10 microM) significantly reduced FA accumulation during ischemia (P less than 0.05), but not during reperfusion (0.05 less than P less than 0.10). Post-ischemic recovery of CO was improved (87 +/- 12%). This was neither associated with preservation of myocardial adenine nucleotide content, nor significant reduction of enzyme release. Mepacrine (1 microM) completely abolished reperfusion arrhythmias and improved recovery of CO (88 +/- 7% of pre-ischemic value). The reduction of FA content in ischemic and reperfused hearts did not reach the level of significance. Enzyme release was not attenuated. At 10 microM, mepacrine completely prevented accumulation of FAs during ischemia and reperfusion, abolished reperfusion-arrhythmias, and reduced enzyme release. No concomitant preservation of adenine nucleotides was observed. In conclusion, nicotinic acid and mepacrine are able to reduce ischemia- and reperfusion-induced changes in myocardial lipid metabolism. In addition, both drugs improve post-ischemic functional recovery. It remains to be established whether these effects are causally related.
Doppler signal processing cannot only be employed to detect the local blood velocity as function of time, but also to assess transcutaneously the displacement of the arterial walls during the cardiac cycle (distension waveform) and, hence, the time-dependent changes in arterial diameter relative to its initial diameter at the start of a cardiac cycle. The distension waveform normalized with respect to the local pulse pressure provides useful information about the local elasticity of the arterial wall. The displacement of the arterial wall can be obtained by processing the RF-signals within a sample volume coinciding with the arterial wall. To evaluate this method a dedicated high-speed memory system has been developed storing the RF-signal, as obtained with a conventional echo-imager in M-mode, over a number of successive sweeps covering a selected depth range. The data are transferred line after line to a personal computer (PC) and processed on the fly, thereby relieving the memory requirements of the PC. It can be concluded that a RF-signal memory in combination with a PC provides a useful tool to extract detailed diameter waveforms from the RF-signals obtained. Although the system does not process the signals in real-time the process can be considered to be on-line since the results become available within one minute after the acquisition of the data is completed.
To determine whether postoperative oedema could be predicted preoperatively by microcirculatory parameters, we studied nutritive capillary blood flow in 21 patients before and after limb salvage procedures. All patients had severe lower limb ischaemia and underwent femoro-popliteal or femoro-crural bypass surgery. The systolic ankle-branchial arm index and systolic toe pressure were used as macrocirculatory parameters. Intravital capillary microscopy was used to measure red blood cell (RBC) and peak RBC velocity and time to peak RBC velocity after release of a 1 min arterial occlusion in the nailfold of the toe. Transcutaneous pO2 was measured on the dorsum of the foot at rest, during oxygen inhalation and following a release of a 5 min occlusion. After surgery the mean systolic ankle-brachial index and systolic toe pressure and all transcutaneous pO2 parameters improved significantly (P less than 0.001). Mean peak RBC velocity increased from 0.156 mm/s to 0.310 mm/s (P less than 0.05), indicating that the reactive hyperaemic response in the capillary bed had improved. Eleven patients developed postoperative oedema. There were no differences in postoperative macro and microcirculatory parameters between the patients with oedema (n = 11) and those without oedema (n = 10). However, preoperatively RBC velocity and peak RBC velocity were significantly lower (P less than 0.05) and time to peak RBC velocity was significantly longer (P less than 0.01) in patients who developed oedema. These findings show that in patients with severe limb ischaemia vascular surgery improves both macro- and microcirculatory blood flow, but that these patients develop oedema after vascular surgery when microcirculatory blood flow is compromised preoperatively.
Increased vascular resistance in spontaneous hypertension has been attributed to a reduced arteriolar lumen and a decrease in the number of arterioles and capillaries. In the present study, microvascular mechanisms for increased resistance were investigated in the cremaster muscle of 5-6-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) using intravital microscopy. Vessels were classified on the basis of their location in the network relative to their branching order and function (A1-A4). In each preparation, one vessel of each category was observed for its side-branches, using bright-field microscopy. By comparing the number of side-branches seen under control conditions and after maximal vasodilatation (10(-3) mol/l adenosine, topically) we assessed their functional reserve. Capillary density was investigated using incident fluorescence microscopy. Both under control conditions and after vasodilatation, mean arterial pressure and heart rate were increased in SHR (mean arterial pressure: SHR 103 +/- 4 mmHg, WKY 89 +/- 3 mmHg, P less than 0.05; heart rate: SHR 380 +/- 16 beats/min, WKY 343 +/- 12 beats/min, P less than 0.05). Arterioles (A1-A4) of SHR and WKY were equal in diameter (SHR: 75.8 +/- 3.2, 48.7 +/- 1.1, 21.4 +/- 0.9, 10.0 +/- 0.04 microns; WKY: 71.6 +/- 2.4, 48.9 +/- 1.1, 18.5 +/- 0.9, 9.8 +/- 0.3 microns; A1-A4, respectively). After adenosine, the relative increase in diameter was similar in both groups. The number of side-branches under control conditions was similar in A1 and A2 vessels. SHR had fewer A3 vessels per A2 and fewer A4 vessels per A3 (per unit length), indicating a diminished arteriolar reserve.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of chronic administration of verapamil, following a double-blind, crossover protocol, on the distensibility and cross-sectional compliance of the common carotid artery was investigated in 19 patients with essential hypertension. Distensibility was significantly increased during verapamil treatment as compared to placebo for both left and right common carotid artery (p less than 0.01 and p less than 0.05, respectively). The cross-sectional compliance was significantly increased during verapamil treatment for the right common carotid artery (p less than 0.05). For the left common carotid artery, the difference did not reach the level of significance (p = 0.16). The common carotid artery diameter and the arterial pulse pressure were not significantly different during verapamil treatment as compared with placebo. The results of this study indicate that chronic treatment with verapamil increases distensibility and cross-sectional compliance of the common carotid artery in hypertensive subjects. These improvements have to be considered as changes in arterial wall properties because no significant differences in pulse pressure and diameter could be detected between the verapamil and placebo periods. Improved arterial wall properties could result in a better management of the flow jet from the heart, and might protect the patients from atherosclerotic complications of hypertension.
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Changes in the vasomotion waveform were studied in transverse arterioles (TAs) and their first-order side branches (FOSs) in the tenuissimus muscle of 14 young, anesthetized rabbits during stepwise arterial pressure reduction and local application of adenosine using intravital video microscopy. Pressure reduction resulted in a systematic increase in vasomotion cycle length (CL) and amplitude (A) concomitant with an increase in effective vascular diameter (Deff) and maximum diameter and a decrease in blood flow (Q). During adenosine application Deff and maximum diameter also increased, but CL and A did not change systematically. At moderate pressure reductions and during adenosine application CL changes were limited (less than 1.5 s) and nonsystematic, agreeing with an earlier study (D. W. Slaaf, G. J. Tangelder, H. C. Teirlinck, and R. S. Reneman. Microvasc. Res. 33: 71-80, 1987). In TAs these changes resulted from changes in both the dilation and the constriction phase. In FOSs, however, changes in CL were caused by prolongation of the dilation phase alone. At greatly reduced pressure levels, the CL increase was more pronounced and in both TAs and FOSs was caused by plateau formation in the dilation phase. Stretch of the arteriolar wall does not seem to play a role in control of the vasomotion waveform. Because the onsets of dilation always occur synchronously in TAs and FOSs, but the onsets of constriction do not, vasomotion seems to be a series of rhythmic dilations.