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Biomedical subjects

R S Reneman

Publications and source records attributed to R S Reneman.

At least 127 records · Page 7Linked to original sources

Creation of a distal arteriovenous fistula improves microcirculatory hemodynamics of prosthetic graft bypass in secondary limb salvage procedures.

PURPOSE: In patients with critical limb ischemia, poor distal arterial runoff, and absence of autogenous veins, the use of an artificial graft and an arteriovenous fistula might be a valuable option. However, in these patients little information is available regarding preoperative and postoperative microcirculatory hemodynamics after this type of intervention. METHODS: With the use of intravital capillary microscopy, we studied the effect of distal revascularization on the microcirculation in 26 patients with critical limb ischemia. All patients had had failed vascular reconstructive operations, and artificial grafts were required because of the absence of autogenous veins. Patients were prospectively investigated and divided into two groups: 12 patients received a femorocrural bypass with polytetrafluoroethylene grafts, and 14 patients underwent the same procedure with the creation of an arteriovenous fistula at the site of the distal anastomosis and ligation of the proximal vein. Red blood cell velocity was measured before and after arterial occlusion to determine microcirculatory hemodynamic alterations. RESULTS: Immediate postoperative graft patency was achieved in all 26 patients. The 1-year cumulative graft patency rate was 64% in the group that had creation of an arteriovenous fistula, which was significantly higher (p < 0.01) compared with that in the group in which a fistula was not created (21%). The 1-year cumulative foot salvage rate was 72% in the patients with an arteriovenous fistula and 43% in the patients without a fistula (p < 0.05). Red blood cell velocity increased similarly in both groups after the bypass procedure. Peak and time to peak red blood cell velocity also improved significantly in both groups; however, comparing both groups, peak and time to peak red blood cell velocity were significantly better (p < 0.05) in the patients with an arteriovenous fistula and remained significantly higher during the follow-up period. CONCLUSIONS: In conclusion, creation of an adjunctive arteriovenous fistula at the distal anastomosis of a prosthetic graft appears to improve microcirculatory hemodynamics in the nutritional capillary vascular bed. Improved graft patency and foot salvage rates suggest that this procedure benefits patients with critical limb ischemia who have no usable veins.

Adult↗

Differences in ischaemia tolerance between hypertrophied hearts of adult and aged spontaneously hypertensive rats.

OBJECTIVE: The aim was to examine differences between the postischaemic functional and biochemical recovery of adult and aged hypertrophied hearts. METHODS: Isolated hypertrophied hearts of adult and aged spontaneously hypertensive rats (SHRadult; SHRaged) and normal hearts of age matched Wistar-Kyoto rats (WKYadult; WKYaged) were perfused in an ejecting heart preparation. Haemodynamic function was monitored before and after 45 min of ischaemia. Coronary effluent samples and tissue biopsies were taken for biochemical analysis. RESULTS: After ischaemia, in SHRadult and WKYadult the maximum positive first derivative of the left ventricular pressure (dP/dtmax) was restored to 105% and 97% respectively of the preischaemic values. Left ventricular developed pressure recovered to 80% (SHRadult) and 97% (WKYadult), while cardiac output reached 71% (SHRadult) and 99% (WKYadult) of preischaemic levels. In SHRaged and WKYaged the dP/dtmax recovered to 26% and 60% respectively (both p < 0.05 compared to the preischaemic values). The left ventricular developed pressure recovered to 36% in SHRaged and to 73% in WKYaged (both p < 0.05), while cardiac output was restored to 6% in SHRaged and 38% in WKYaged (both p < 0.05). Throughout reperfusion, left ventricular end diastolic pressure remained significantly elevated in SHRaged, and was associated with a prominent subendocardial underperfusion, suggesting an impaired diastolic functional recovery. Overall haemodynamic recovery was significantly better in the WKYaged than in the SHRaged. The preischaemic total adenine nucleotides content was comparable in all groups, but creatine phosphate levels were significantly lower in both aged groups than in adult groups. In all but the WKYadult, the total adenine nucleotides were depressed upon reperfusion, while creatine phosphate normalised, except in SHRaged. SHRaged lost more lactate dehydrogenase and tended to lose more xanthine and uric acid than other groups. CONCLUSIONS: The aged hypertrophied heart shows a higher vulnerability to ischaemic damage than the adult hypertrophied heart. This phenomenon is associated with subendocardial underperfusion, increased membrane damage and inadequate recovery of creatine phosphate levels.

Adenosine Diphosphate↗

Faster ageing of the carotid artery bifurcation in borderline hypertensive subjects.

OBJECTIVES: It has been suggested that arteries age more quickly in borderline hypertensives (BHT) than in normotensives. If this hypothesis is correct, the decrease in distensibility and compliance in the carotid artery bifurcation should be most pronounced in the carotid artery bulb, because this site is known to be the most affected by age. DESIGN: Arterial distensibility was measured non-invasively by means of an ultrasound vessel wall moving-detector system at various sites along the carotid artery bifurcation in BHT and normotensive controls. METHODS: Sixteen bifurcations of male BHT (mean age 38 years) and 15 bifurcations of normotensive age-matched controls (NTO) were studied in subjects from a population study on borderline hypertension. To evaluate age-related changes, 18 bifurcations of normotensive young male subjects (NTY; mean age 24 years) were included in the study. RESULTS: In NTY subjects no significant variations in distensibility were found along the carotid artery bifurcation, but in NTO subjects the proximal and distal parts of the carotid artery bulb were significantly less distensible than the common carotid artery. In BHT the distensibility was significantly lower at all levels in the bulb than in the common carotid artery, and its proximal part was significantly stiffer than the rest of the bulb. CONCLUSIONS: The findings in this study indicate faster ageing of the carotid artery bifurcation in male BHT than in normotensives of comparable age. In particular, the proximal part of the carotid artery bulb, where the baroreceptors are predominantly located, is most affected by the disease.

Adult↗

Production of arachidonic acid metabolites in adult rat cardiac myocytes, endothelial cells, and fibroblast-like cells.

Cells were incubated in the presence of the Ca2+ ionophore A23187 (10 microM) and arachidonic acid (AA, 80 microM). The release of eicosanoids from subcultivated cardiac endothelial and fibroblast-like cells amounted to 23.3 +/- 4.5 and 2.0 +/- 0.4 nmol/mg cellular protein per 30 min, respectively. The release from isolated cardiomyocytes remained below the detection limit of the high-performance liquid chromatography assay (< 0.00015 nmol/assay). When a very sensitive radioimmunoassay was applied, cardiomyocytes released 0.002 +/- 0.0001 nmol prostacyclin per milligram cellular protein per 30 min. Prostaglandin (PG) E2 and PGF2 alpha, 12-hydroxyheptadecatrienoic acid, 11- and 15-hydroxyeicosatetraenoic acid, and thromboxane B2 were the main eicosanoids released by endothelial cells. The stable product of prostacyclin, 6-keto-PGF1 alpha, contributed relatively little to the total amount of eicosanoids formed by endothelial cells. Fibroblast-like cells released predominantly PGE2 and 6-keto-PGF1 alpha and, to a lesser extent, 12-hydroxyheptadecatrienoic and 15-hydroxyeicosatetraenoic acids. Neither endothelial cells nor fibroblast-like cells released leukotrienes. A23187 stimulated eicosanoid release from endothelial cells when exogenous AA was below 40 microM. Addition of albumin reduced the amount of eicosanoids produced. Histamine and bradykinin did not influence 6-keto-PGF1 alpha and PGE2 production in cardiomyocytes. Histamine only gave rise to a slight but significantly higher release of 6-keto-PGF1 alpha in endothelial cells.

6-Ketoprostaglandin F1 alpha↗

Subepicardial fiber strain and stress as related to left ventricular pressure and volume.

In a mathematical model of the mechanics of the left ventricle (LV) by Arts et al. (1), assuming uniformity of fiber stress (sigma f) and fiber strain (delta epsilon f) in the wall during the ejection phase, fiber stress and fiber strain were related to LV cavity pressure (Plv), LV cavity volume (Vlv) and wall volume (Vw) by the following pair of equations: sigma f = Plv (1 + 3 Vlv/Vw) and delta epsilon f = 1/3 delta ln (1 + 3 Vlv/Vw). The ratio of Vlv to Vw appeared to be the most important geometric parameter, whereas the actual LV shape was of minor importance. The relationships on fiber strain and stress were evaluated experimentally in six anesthetized open-chest dogs during normal and elevated (volume loading) end-diastolic LV pressure. Subepicardial fiber strain was measured simultaneously in 16 adjacent regions of the LV anterior wall, using optical markers that were attached to the epicardial surface and recorded on video. Changes in Vlv were measured by use of four inductive coils sutured to the LV in a tetrahedric configuration. Vw was measured postmortem. During control as well as hypervolemia the following results were found. At the anterior free wall of the LV, the slope of the estimated linear relationship between measured and calculated fiber strain was 1.017 +/- 0.168 (means +/- SD), which is not significantly different from unity. Calculated fiber stress corresponded qualitatively and quantitatively with experimental results reported on isolated cardiac muscle. Calculated subepicardial contractile work per unit of tissue volume was not significantly different from global pump work as normalized to Vw. These findings support the assumption of homogeneity of muscle fiber strain and stress in the left ventricular wall during the ejection phase. Furthermore, average values of fiber stress and strain can be estimated on the basis of measured left ventricular pressure and volume.

Animals↗

Long-term effects of recombinant human erythropoietin on macro- and microcirculation in chronic hemodialysis patients.

Recombinant human erythropoietin therapy (ReHuEpo) at short term leads to an increase in systemic vascular resistance and to a decrease in cardiac index and skin microcirculatory flow. Long-term adaptive changes might occur. We studied the effects of ReHuEpo therapy on macrocirculation and skin microcirculation in 8 normotensive and normovolemic hemodialysis patients before and after, respectively, 4 and 14 months of treatment. The reported macrocirculatory changes at short term were at long term not significantly different as compared with the initial values. The mean arterial pressure remained unaltered, as might be explained by the slow correction of the hematocrit and the decrease in cardiac output in all initially long-lasting normotensive patients who were maintained normovolemic. Left ventricular end-diastolic dimensions decreased, and also the left ventricular muscle mass decreased, depending on the initial left ventricular muscle mass. The skin oxygenation improved, whereas the maximal capillary flow decreased both at short- and long-term ReHuEpo treatment. The number of capillaries in the nail fold remained unchanged. However, the percentage of tortuosity decreased significantly during ReHuEpo therapy.

Adult↗

Annexins in cardiac tissue: cellular localization and effect on phospholipase activity.

Stimulation of cardiac phospholipid metabolism has diverse biological effects, ranging from subtle changes in cellular function to severe cellular damage. Accordingly, knowledge of the factors governing the activity of cardiac phospholipases is of great biological importance. A possible role of annexins, intracellular proteins that bind to membranes in a calcium dependent manner, as modulators of phospholipase activity has been proposed. In this study we investigated the cell type specific distribution of Annexin V and VIII in the heart. Recombinant Annexin V was used to examine the effect of this type of Annexin on cardiac phospholipase activity. Western blot analysis shows that annexin V is abundantly present in the heart. Using isolated myocytes and cultured cardiac endothelial and fibroblast-like cells, it is demonstrated that the localization of Annexin V is confined to non-myocytes. No positive bands matching the Mw of recombinant Annexin VIII are found in any of the cell types examined. In vitro studies demonstrate that recombinant Annexin V potently inhibits the activity of cardiac membrane-bound phospholipases, acting on their natural surrounding substrate, in a calcium dependent manner. Interestingly, annexin V also inhibits triacylglycerol hydrolysis. In conclusion, the expression of annexins is cell-type specific and suggests a cell-type specific function of these proteins in the heart. The absence of Annexin V in cardiac myocytes dismisses involvement of this annexin in cardiomyocyte phospholipid metabolism. The presence of Annexin V in cardiac endothelial and fibroblasts suggests a regulating role in the phospholipid homeostasis of non-myocyte cell types in the heart.

Animals↗

Description of the deformation of the left ventricle by a kinematic model.

A model of left ventricular (LV) kinematics is essential to identify the fundamental physiological modes of LV deformation during a complete cardiac cycle as observed from the motion of a finite number of markers embedded in the LV wall. Kinematics can be described by a number of modes of motion and deformation in succession. An obvious mode of LV deformation is the ejection of cavity volume while the wall thickens. In the more sophisticated model of LV kinematics developed here, seven time-dependent parameters were used to describe not only volume change but also torsion and shape changes throughout the cardiac cycle. Rigid-body motion required another six parameters. The kinematic model employed a deformation field that had no singularities within the myocardium, and all parameters describing the modes of deformation were dimensionless. Note that torsion, volume and symmetric shape changes all require the definition of a cardiac coordinate system, which has generally been related to the measured cardiac geometry by reference to approximate anatomical landmarks. However, in the present study the coordinate system was positioned objectively by a least-squares fit of the kinematic model to the measured motion of markers. Theoretically, at least five markers are needed to find a unique set of parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dependence of local left ventricular wall mechanics on myocardial fiber orientation: a model study.

The dependence of local left ventricular (LV) mechanics on myocardial muscle fiber orientation was investigated using a finite element model. In the model we have considered anisotropy of the active and passive components of myocardial tissue, dependence of active stress on time, strain and strain rate, activation sequence of the LV wall and aortic afterload. Muscle fiber orientation in the LV wall is quantified by the helix fiber angle, defined as the angle between the muscle fiber direction and the local circumferential direction. In a first simulation, a transmural variation of the helix fiber angle from +60 degrees at the endocardium through 0 degrees in the midwall layers to -60 degrees at the epicardium was assumed. In this simulation, at the equatorial level maximum active muscle fiber stress was found to vary from about 110 kPa in the subendocardial layers through about 30 kPa in the midwall layers to about 40 kPa in the subepicardial layers. Next, in a series of simulations, muscle fiber orientation was iteratively adapted until the spatial distribution of active muscle fiber stress was fairly homogeneous. Using a transmural course of the helix fiber angle of +60 degrees at the endocardium, +15 degrees in the midwall layers and -60 degrees at the epicardium, at the equatorial level maximum active muscle fiber stress varied from 52 kPa to 55 kPa, indicating a remarkable reduction of the stress range. Moreover, the change of muscle fiber strain with time was more similar in different parts of the LV wall than in the first simulation. It is concluded that (1) the distribution of active muscle fiber stress and muscle fiber strain across the LV wall is very sensitive to the transmural distribution of the helix fiber angle and (2) a physiological transmural distribution of the helix fiber angle can be found, at which active muscle fiber stress and muscle fiber strain are distributed approximately homogeneously across the LV wall.

Computer Simulation↗

Assessment of the microcirculation provides additional information in critical limb ischaemia.

Systolic ankle and toe pressure measurements are considered to be the best way of documenting arterial occlusive disease. In the European consensus, chronic critical limb ischaemia is defined as persistent pain with an ankle pressure lower than 50 mmHg. To investigate the possible adjunct value of microcirculatory assessment, capillary microscopy and transcutaneous oximetry were performed in 21 asymptomatic persons (F1), 89 claudicants (F2) and 54 patients with critical limb ischaemia (F3/4). Capillary morphology (diameter, density) and dynamics [red blood cell velocity (RBCV), peak RBCV and time to peak RBCV], as well as transcutaneous oximetry parameters were determined for each Fontaine group and compared with ankle and toe pressure measurements. Despite considerable overlap, ankle and toe pressures were significantly (p less than 0.001) different between F1, F2 and F3/4 patients. Capillary density (p less than 0.05), diameter (p less than 0.05), peak RBCV (p less than 0.05) and time to peak RBCV (p less than 0.01), as well as transcutaneous oximetry parameters (p less than 0.001) were significantly different between all groups and impaired with progression of ischaemia. However, a similar overlap between all groups was observed, except the supine TcpO2 parameter which separated F3/4 patients completely from the other groups. In all patients with critical limb ischaemia, dynamic parameters, such as peak RBCV (p less than 0.01) and time to peak RBCV (p less than 0.001), were significantly lower as compared to non-critically ischaemic patients, irrespective of an ankle pressure below or above a value of 50 mmHg, illustrating the additional value of microcirculatory assessment in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Microvascular reactivity differences between the two legs of patients with unilateral lower limb ischaemia.

Posturally induced microvascular constriction in the skin of the leg is disturbed in severe ischaemia. It is unknown whether this disturbance is of local or central origin and whether the stage of ischaemia at which this disturbance occurs differs when the nutritive and thermoregulatory flow levels are compared. We investigated the effect of posture on the skin microcirculation in 21 patients with unilateral severe ischaemia. The results were compared with those from the contralateral, asymptomatic leg and with results from 11 age-matched controls. Patients were investigated in supine and sitting positions, using capillary microscopy to measure nutritive flow, and laser Doppler fluxmetry (LDF) to measure thermoregulatory flow, of the big toes. In the supine position, capillary flow and LDF were lower in the diseased than in the asymptomatic and control legs. After changing from the supine to the sitting position, capillary perfusion decreased in all three groups, but was most pronounced in the controls. Laser Doppler flux decreased in the controls, but increased in the diseased legs, suggesting disturbed vasoconstriction mechanisms in the deeper skin microvessels. These findings indicate that in severe limb ischaemia, posturally induced microvascular reactivity is sustained at the nutritive level but not at the thermoregulatory level. This disturbed reactivity is considered a local phenomenon, as it is not observed in the contralateral leg.

Adult↗

The relevance of posturally induced microvascular constriction after revascularisation in patients with chronic leg ischaemia.

In patients with severe chronic lower limb ischaemia, postural vasoconstriction is disturbed, resulting in enhanced skin microcirculatory perfusion on leg dependency. After vascular reconstructive surgery, postoperative oedema formation is frequently seen. In 31 patients with leg ischaemia undergoing revascularisation we investigated whether and, if so, for how long after surgery postural vasoconstriction would take to recover, and whether disturbed vasoconstriction correlates with the occurrence of postoperative oedema. Capillary microscopy and laser Doppler fluxmetry were used to assess nutritional and total skin perfusion, respectively. The measurements were performed before and up to 37 days after surgery. After revascularisation, the mean ankle blood pressure index rose from 40 to 82%. All patients, except those with persistently disturbed vasoconstriction showed improved microcirculatory parameters. Postural vasoconstriction was restored in 24 patients, occurring approximately on the eighth postoperative day. All patients who failed to recover vasoconstriction developed postoperative oedema. This study shows that the disturbance in postural vasoconstriction can be reversible, probably due to recovery of arteriolar smooth muscle tone, and that patients with persistently disturbed postural vasoconstriction, are prone to develop postoperative oedema.

Adult↗

The time sequence of electrical and mechanical activation during spontaneous beating and ectopic stimulation.

The relation between the sequence of electrical (E) and mechanical (M) activation was studied at the LV anterior wall of open-chest dogs (n = 11). M activation was defined as the onset of epicardial fibre shortening, as measured with a recently developed video technique. E activation was determined with a brush of extracellular electrodes. The delay between activation of basal and apical regions was consistently larger for M activation than for E activation: during spontaneous beating: 20.5 +/- 7.30 ms vs 8.8 +/- 3.31 ms, during right ventricular outflow tract pacing: 50.3 +/- 7.69 ms vs 39.0 +/- 5.31 ms and during left ventricular apex pacing 40.1 +/- 10.03 ms vs 25.4 +/- 9.30 ms, respectively (P less than 0.05 in all cases). The E-M time interval was consistently shorter in early than in late activated regions: 32 +/- 10 vs 41 +/- 8 ms during RV outflow tract pacing (P = 0.09) and 24 +/- 30 vs 40 +/- 24 ms during LV apex pacing (P less than 0.05). Electrical asynchronies larger than 40 ms resulted in decreases of systolic blood pressure and stroke volume. This study shows that the asynchrony of cardiac motion exceeds that of electrical activation because the time interval between electrical activation and onset of fibre shortening is larger the later a particular region is activated. Possible explanations for this phenomenon are discussed.

Animals↗

Concentration profile of blood platelets differs in arterioles and venules.

Platelet distribution was investigated in 21 venules (V) and 10 arterioles (A) of the rabbit mesentery (vessel diam 15-33 microns). Circulating platelets were labeled in vivo with the dye acridine red and observed with fluorescence video microscopy. Only platelets flowing in a thin (5-7 microns) optical section located about the median plane of the vessel were used. The relative position of each platelet, i.e., the distance of its centroid to the left vessel wall divided by the local vessel diameter, was determined. In addition, in 10 venules leukocyte margination was inhibited by intravenous injection of dextran sulfate (500,000 mol wt; 30 mg/kg body wt). The number of platelets per unit volume (i.e., platelet density) relative to the mean density was significantly higher in the vessel center of V (1.04) than of A (0.55; P less than 0.005). In contrast, near the wall this density was significantly higher in A compared with V. Mean values were as follows: at radial position (R) = 0.9-1.0, 0.30 in A and 0.11 in V (P greater than 0.05); at R = 0.8-0.9, 1.63 in A and 0.84 in V (P less than 0.002); at R = 0.7-0.8, 1.60 in A and 1.36 in V (P greater than 0.05); at R = 0.6-0.7, 1.16 in A and 1.60 in V (P less than 0.02); and at R = 0.5-0.6, 0.92 in A and 1.36 in V (P less than 0.02). These differences in platelet distribution between arterioles and venules are not caused by the presence of leukocyte margination in venules.

Animals↗

Porous medium finite element model of the beating left ventricle.

The axisymmetric model described represents myocardial tissue as a spongy anisotropic viscoelastic material. It includes torsion around the axis of symmetry of the ventricle, transmural variation of fiber angle, and redistribution of intracoronary blood in the myocardial wall. In simulations, end-systolic principal strains were equal to 0.45, -0.01, and -0.24 at two-thirds of the wall thickness from the epicardium and 0.26, 0.00, and -0.19 at one-third of the wall thickness from the epicardium. The direction of maximal shortening varied by less than 30 degrees from epicardium to endocardium, whereas fiber direction varied by greater than 100 degrees from epicardium to endocardium. During a normal cardiac cycle peak, equatorial intramyocardial pressure differed by less than 5% from peak intraventricular pressure. When redistribution of intracoronary blood in the ventricular wall was suppressed, peak equatorial intramyocardial pressure was found to exceed peak intraventricular pressure by greater than 30%. Simulated contraction of an unloaded left ventricle (left ventricular pressure = 0 kPa) produced similar magnitude for systolic intramyocardial pressures as the normal cardiac cycle. Transmural systolic fiber stress distribution was very sensitive to the chosen transmural fiber angle distribution.

Animals↗

Capillary recruitment and pain relief on leg dependency in patients with severe lower limb ischemia.

BACKGROUND: Patients suffering from severe lower limb ischemia may experience pain relief on leg dependency despite the fact that dependency normally results in arteriolar vasoconstriction. To clarify this possible paradox, skin microcirculation of the limb was investigated in 75 patients with different stages of lower limb ischemia and in 12 asymptomatic subjects. METHODS AND RESULTS: Using nailfold capillary video microscopy, red blood cell-perfused capillary density and diameter and red blood cell velocity were assessed in supine and sitting positions. Capillary density increased by changing from the supine to the sitting position, especially in patients with limb-threatening ischemia (showing a 4.5-fold increase versus a 1.5-fold increase in asymptomatic subjects). In subjects without or with mild ischemia, capillary perfusion was two to four times lower in the sitting than in the supine position. In patients with limb-threatening ischemia, perfusion was strongly reduced, being slightly higher in the sitting position. Patients with relief of pain while sitting did not always have a higher capillary perfusion but did have a higher capillary density in the sitting position. CONCLUSIONS: The arteriolar postural vasoconstrictive mechanism at the nutritive level is still intact in subjects without or with mild ischemia but not in patients with severe ischemia. Capillary recruitment rather than disturbed arteriolar vasoconstriction could explain why patients with severe leg ischemia prefer leg dependency.

Adult↗