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Biomedical subjects

C Mrowietz

Publications and source records attributed to C Mrowietz.

At least 19 recordsLinked to original sources

Influence of extra corporeal circulation on myocardial oxygen tension: results of an animal model.

BACKGROUND: Experimental data have shown the potential risk of cellular damage of the myocardium during extra corporeal circulation (ECC). The influence of ECC on myocardial oxygen tension however remained unclear. Therefore, the influence of ECC on the oxygen tension in a beating heart was investigated. METHODS: In a pig animal model flexible pO2 microcatheters were positioned in the midmyocardium of the left ventricle and the skeletal muscle and tissue oxygen tension during ECC were monitored and compared with data of a control group without ECC. RESULTS: ECC and unload of the heart caused a significantly higher increase of myocardial pO2 than in a non-ECC control group. CONCLUSION: Our findings show the beneficial effect of ECC on myocardial pO2. This may support the use of ECC in coronary artery bypass grafting because the potential myocardial injury due to ECC is not related to myocardial ischemia. On the contrary, myocardial pO2 was even increased during extracorporeal circulation in this study.

Animals↗

Effect of desmopressin (DDAVP) on platelet membrane glycoprotein expression in patients with von Willebrand's disease.

When patients with von Willebrand's disease were given a single injection of desmopressin (0.4 microg/kg body weight), there was a considerable increase in platelet reactivity (from 0.95 +/- 0.19 to 1.44 +/- 0.42; p = 0.0033). On flow cytometry, increased glycoprotein Ib/IX expression in the platelets was found after the desmopressin injection; when phycoerythrin-marked anti-CD62 antibodies were used, the mean fluorescence rose from 428.9 +/- 56.6 to 440.7 +/- 51.4 (p = 0.0056), and from 425.9 +/- 55.0 to 437.4 +/- 53.9 (p = 0.0018) when phycoerythrin-marked anti-thrombospondin antibodies were used. Apart from the rise in the von Willebrand factor, this could explain the increased platelet reactivity. However, the surface expression of CD62, CD63 and thrombospondin on platelets did not change following the desmopressin injection.

Adolescent↗

Haemocompatibility of polymer-coated stainless steel stents as compared to uncoated stents.

Acute and subacute stent thrombosis still represent an unsolved problem in connection with endovascular stents. For this reason coatings are tested now with the intention to reduce thrombogenicity of stainless steel surfaces. This comparative study examined whether a polymeric stent coating affected the haemocompatibility of a stainless steel stent. For compatibility testing, coated and non-coated stents were implanted in a low-grade thrombogenic closed-loop system perfused with platelet rich plasma at shear rates far below the threshold value at which shear-rate-induced activation of thrombocytes occurs. After 21 circulations of the filling volume (exposure time: 6.2 min), the number of single circulating platelets in the perfusion system with uncoated stainless steel stents decreased almost twice as much as was the case with polymer-coated stents. This is thought to indicate that more thrombocytes had adhered to the uncoated stainless steel stent, or that the thrombocytes were clustered in circulating aggregates. Parallel to the platelet aggregation/adherence, a release reaction took place, as was evident from the TAT complexes indicating the generation of thrombin. In the case of the implantation of uncoated stainless steel stents, both the number of activated circulating thrombocytes and the level of platelet reactivity (number of thrombocytes circulating in the plasma as aggregates) were notably higher than in the system with polymer-coated stents. At the same time it should be noted that the activation or aggregation is almost wholly attributable to the exogenic surface of the implanted stent, since activation due to the tube system or to shear rate can be excluded (as shown by measurements of the system without a stent). In addition to activation of the thrombocytes, a notable increase in the number of receptors per platelet (significant only in the system with the uncoated stent) took place. This supports both the adherence of the thrombocytes and their readiness to aggregate, since more receptors (docking places for ligands) are available. The better haemocompatibility of the polymer-coated stents, as verified in the laboratory, was also evident under microscopic examination of the explanted stents following the perfusion tests.

Blood Platelets↗

Effect of LDL apheresis on oxygen tension in skeletal muscle in patients with cardiac allograft vasculopathy and severe lipid disorder.

In this study, the extent to which intramuscular pO2 is influenced by a single HELP-apheresis (Heparin-induced Extracorporeal LDL Precipitation) was investigated in 10 patients with cardiac allograft vasculopathy (CAV) and severe lipid disorder. For this purpose, a sterile flexible pO2 microcatheter was inserted into the anterior tibial muscle and pO2 monitoring was begun 10 minutes before starting apheresis treatment. The intramuscular pO2 values were recorded continuously until the end of apheresis treatment and a subsequent 30-minute further observation phase. The patients with CAV and severe lipid disorder presented with 11.6+/-3.8 mmHg significantly and pathologically reduced intramuscular pO2 (p<0.001). LDL apheresis resulted in a significant increase in pO2 in the anterior tibial muscle. Thirty minutes after the end of HELP-apheresis, intramuscular partial oxygen pressure had increased by 162% and showed values at this point, 30.3+/-9.8 mmHg, similar to those found in healthy subjects.

Blood Component Removal↗

Sildenafil improves cutaneous microcirculation in patients with coronary artery disease: a monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study.

UNLABELLED: Endothelial dysfunction of precapillary arterioles impairs nutritional microcirculation at rest as well as during post-ischemic reactive hyperemia. In this monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study we investigated the acute effect of 50 mg sildenafil, a selective PDE-5 inhibitor, on resting and post-ischemic capillary circulation in twenty patients with angiographically confirmed coronary artery disease not taking nitrates or NO-donors. Mean erythrocyte velocity in digital nail-fold capillaries was determined before and after sildenafil and placebo, both baseline and after a three-minutes supra-systolic occlusion of the upper arm. Primary efficacy parameter was the drug effect on peak velocity during reactive hyperemia (peak velocity: V(max)). Post ischemic maximal capillary erythrocyte velocity V(max) significantly increased by 47% one hour after 50 mg sildenafil (mean value+/-standard deviation: 0.85+/-0.42 mm/s vs. 0.58+/-0.18 mm/s at baseline, p=0.0023), whereas placebo had no effect (p=0.5248). The difference between sildenafil and placebo was significant (p=0.0129) and sildenafil's effect can be regarded as biometrically highly relevant with standardized difference according to Cohen of 0.81. In spite a small decrease of both systolic and diastolic blood pressure after sildenafil, sildenafil significantly increased capillary erythrocyte velocity at rest. CONCLUSION: A single oral dose of sildenafil significantly increased resting and post-ischemic cutaneous capillary circulation in patients with coronary artery disease. Future studies should assess whether sildenafil also improves nutritional capillary blood flow in other organs and in other diseases with impaired endothelial function and microcirculation, for example in diabetic microangiopathy.

3',5'-Cyclic-GMP Phosphodiesterases↗

Blood fluidity, fibrinogen, and cardiovascular risk factors of occlusive arterial disease: results of the Aachen study.

In the Aachen study the prevalence of arterial disease was established in 346 out of a cohort of 2821 subjects between 45 and 65 years of age. Rheological variables and risk factor profile for patients with peripheral occlusive arterial disease (POAD), coronary heart disease (CHD) and cerebrovascular insufficiency (CI) in comparison to a control group are given. Significantly elevated are hematocrit in males, plasma viscosity, erythrocyte aggregation and fibrinogen. It is evident that plasma viscosity is the rheological parameter most often elevated in patients with arterial disease (70.8%). In patients with CI (80.6%) plasma viscosity is elevated about four times more often than in healthy subjects. While 85.8% of healthy volunteers show no or only one elevated rheological parameter only 44.5% of the patients have this constellation. Risk factors are bundled in patients compared to healthy volunteers. 84.2% of the healthy volunteers have no or only one risk factor whereas patients with OAD show this constellation in only 30.9% (32.4% in POAD, 16.1% in CI and 32.4% in CHD).

Blood Viscosity↗

Influence of the direct NO-donor SIN-1 on the interaction between platelets and stainless steel stents under dynamic conditions.

It was investigated whether the NO-donor SIN-1, the active metabolite of molsidomine, influenced the activation of platelets, the formation of circulating platelet aggregates, the spontaneous aggregation of platelets and the activation of the clotting system triggered by a body foreign surface in an in vitro closed-loop perfusion model. With human platelet-rich plasma at micromolar concentrations SIN-1 exerted pronounced effects on the interaction between platelets and an exogenous surface. In the absence of SIN-1, the number of circulating single platelets decreased significantly, which could be due either to the formation of circulating platelet aggregates or to the adhesion of platelets to the stent. Both these processes were blocked by the addition of SIN-1. Moreover, the platelets exhibited hyperaggregability in the absence of SIN-1 whereas the NO-donor was able to completely inhibit spontaneous platelet aggregation. Similar results were obtained in flow cytometry experiments. Without SIN-1, high platelet surface densities of both the GPIb/IX and GPIIb/IIIa receptors were observed. In addition, the density of the fibrinogen receptor increased significantly with the number of perfusion cycles. SIN-1 was able to suppress the augmented GPIIb/IIIa receptor expression significantly. Molsidomine seemed to have the potential to reduce the incidence of thrombotic processes triggered by the exogenous surface of the stent.

Adult↗

Influence of radiographic contrast media on myocardial tissue oxygen tension: NaCl-controlled, randomised, comparative study of iohexol versus iopromide in an animal model.

It was tested whether a bolus injection of 10 ml radiographic contrast medium (iopromide vs. iohexol), compared to a 10 ml NaCl bolus and administered into the left anterior descending artery (LAD) of farm pigs, influenced the tissue pO2 in the territory of this artery. The radiographic contrast media and the NaCl bolus were given in randomised order. The mean pO2 LAD fell from initially 40.3+/-10.9 mmHg to a minimal value of 22.5+/-8.9 mmHg 241+/-44 sec after injecting the iopromide bolus, with this result representing a mean decrease of 44.2% (p=0.0003). The initial pO2 (baseline) was reached again after approximately 10 minutes. The mean pO2 LAD fell from the initial value of 34.5+/-14.6 mmHg to a minimal value of 29.4+/-13.9 mmHg 171.7+/-11.9 sec after injection of the iohexol bolus, with this result representing a mean decrease of 14.8% (p=0.0003). The baseline pO2 was reached again after approx. 5 minutes. The drop in the pO2 after iopromide administration was significantly larger than that after iohexol (p=0.0001), and also the time after which the baseline pO2 is reached again was considerably shorter for iohexol (p=0.001). The two radiographic contrast media did not influence the tissue pO2 in either the territory of the right coronary artery or in skeletal muscle. Injection of a NaCl bolus into the LAD influenced neither the tissue pO2 of the territory of the LAD nor that of the RCA or of the skeletal muscle. The tissue temperature, heart rate and the systolic and diastolic blood pressure were not affected during the three injections. Injection of radiographic contrast media into a coronary artery can lead to a distinct, local microcirculatory impairment in the myocardial territory supplied by this artery. In this case, the extent of the microcirculation impairment seems to depend not only on the viscosity of the contrast media but rather also on its chemotoxicity.

Animals↗

Effect of naftidrofuryl on intramuscular partial oxygen pressure (pO2) prior to, during and after physical load on the treadmill in apparently healthy subjects.

Previous studies demonstrated that naftidrofuryl increased the cutaneous and intramuscular tissue pO2 at rest. The presented open prospective pilot study is to investigate in apparently healthy subjects (n=12) whether naftidrofuryl also affects pO2 in situations of muscular stress. The pO2 is measured with a flexible probe in the anterior tibial muscle during treadmill exercise prior to and after one-week treatment with 100 mg of naftidrofuryl administered three times a day. The intake of naftidrofuryl proved to significantly affect the intramuscular partial oxygen pressure. With 38.6+/-22.9 mmHg, the pO2 is at rest already significantly (p<0.05), i.e., approx. 40% higher after one week of intake than before treatment (27.3+/-12.1 mmHg). This higher pO2 level is maintained during exercise. The higher the physical load, the larger the difference in pO2. While under naftidrofuryl treatment the measured pO2 values exhibit the tendency to increase during the first exercise phase (at a load of 3 km/h and a gradient 5 degree), the differences are even significant under higher physical stress (at 5 km/h and a gradient of 10 degree). With 33.9+/-12.0 mmHg the mean minimum pO2 determined at the higher load level still ranges above the basal pO2 measured before the start of naftidrofuryl treatment.

Adult↗

Primary cutaneous microangiopathy in heart recipients.

In this study we investigated whether a disturbance in microcirculation is detectable in heart recipients with cardiac allograft vasculopathy (CAV) and severe hypercholesterolemia (n = 11) and in 7 heart recipients without CAV in comparison to patients with severe coronary artery disease (n = 49) and age-matched apparently healthy subjects (n = 100). For this purpose, the flow velocity of erythrocytes through cutaneous capillaries at the nail fold of the finger was measured under resting conditions. In addition, reactive hyperemia in the same capillaries after a 3-min ischemia was determined. Patients with CAV and severe lipid disorder showed a pathological reduction in mean capillary erythrocyte velocity under resting conditions with v(RBC) = 0.10 +/- 0.07 mm/s. The latter was significantly and relevantly lower than in patients with coronary three-vessel disease (v(RBC) = 0.46 +/- 0.35 mm/s). It was notable that under resting conditions temporary cessation of flow occurred in 8 of the 11 patients which did not occur in healthy subjects and rarely in patients with three-vessel disease (1 of 49 patients). In comparison to age-matched healthy subjects (v(max) = 1.46 +/- 0.52 mm/s), the patients with three-vessel disease showed a significant reduction in postischemic maximum erythrocyte velocity (v(max) = 0.85 +/- 0.55 mm/s), with a considerable shortening of the duration of reactive hyperemia. Patients with CAV demonstrated a total loss of postischemic reactive hyperemia (only 1 of the 11 patients presented a weak reactive hyperemia). Since no macroangiopathy was detectable in the upstream arm arteries, primary cutaneous microangiopathy can be assumed in patients with cardiac allograft vasculopathy and severe hypercholesterolemia.

Adult↗

Effects of an onion-olive oil maceration product containing essential ingredients of the Mediterranean diet on blood pressure and blood fluidity.

Twenty-four patients with arterial hypertension (WHO class I) received either 4 capsules of an onion-olive oil maceration product, containing essential ingredients of the Mediterranean diet, or placebo daily over a period of one week. In order to investigate the acute effect on arterial blood pressure, measurements were performed before and 5 h after the administration of the first dose of 4 capsules verum or placebo, respectively. For the evaluation of the long term effect further blood pressure measurements were performed after one week's treatment with a daily dose of 4 capsules. After a wash-out phase of 2 weeks followed by a crossover, the second study phase, which was identical in design, was carried out. In addition patients were instructed to measure their blood pressure 4 times daily at home for the whole study period. Haemorheological parameters (platelet aggregation, erythrocyte aggregation, plasma viscosity and haematocrit) were also determined at the measuring points mentioned above. The onion-olive oil maceration product led to a significant decrease in systolic blood pressure. There was also a trend towards a decrease in diastolic blood pressure. The improved blood fluidity observed resulted from a decrease in haematocrit. All effects could be shown immediately and after one week's administration.

Adult↗

Light and scanning-electron microscopic examination of coronary stents in a perfusion-model. Effects of an NO-donor/quantitative analysis.

Does a NO-donor (Corvaton, Aventis, France) attenuate the adherence and the aggregation of platelets in a closed-loop perfusion modell with or without the implantation of coronary stents? SIN-1, the active metabolite of molsidomine, exerted a strong influence on the interaction of platelets with the surfaces of stents. When SIN-1 was added the adherence of platelets to the surfaces of stents was markedly reduced. The sites were most of the platelets adhered to, also changed. More platelets adhered to the stent backbone and less to the free modular stent parts. The localisation of adherent platelets could easily be shown by light microscopy. The aggregation of platelets, accompanied by a spheroidic shape change, could be demonstrated by scanning electron microscopy on the addition of an NO-donor, not only a reduction of platelet adherence was realised but also the reduction of platelet aggregation.

Blood Platelets↗

Peripheral microcirculation during pregnancy and in women with pregnancy induced hypertension.

During pregnancy the cardiovascular system undergoes several changes so as to adapt the maternal organism to the strains of pregnancy. These adaptations can assume a pathological development in persons with a previous history of cardiovascular problems. On the other hand the absence of these adaptations may lead to a pathological course of pregnancy. Pregnancy induced hypertension (PIH) may be such a pathological development due to maladaptation. The causes are for the most part unknown. For some time it has been assumed that it is due to microcirculatory disorders. Using periungual capillary microscopy the present study prospectively investigated the changes in peripheral microcirculation during pregnancy focussing on pregnancy induced hypertension. Sixty-seven women with a normal course of pregnancy and 28 women with pregnancy induced hypertension were evaluated. Throughout the prospective study 3 examinations were performed during pregnancy and one during childbed. The women who developed a PIH were registered during the third trimester. Erythrocyte velocity at rest and vascular reagibility of capillaries following a 3 minute ischaemia were evaluated. In the course of pregnancy a significant increase of approximately 30% in erythrocyte velocity could be observed. Interpolation to obtain the best strait line result demonstrates that it is a continuous increase. Erythrocyte velocity returns to normal in the course of 14 weeks post partum. Due to a physiological vasodilatation during pregnancy, vascular reaction to ischaemic stress significantly decreases. During childbed these changes return to normal. Examinations on women with pregnancy induced hypertension not only showed a significant reduction of microcirculation under resting conditions but also a different pattern of reaction to ischaemic stress. Erythrocyte velocity under resting conditions lies 36% below normal values. Furthermore the distinctly shortened hyperaemic period indicates a hightened sensitivity to vasoconstrictive substances in women with PIH. While taking into account the clinical data a positive correlation with the severity of the illness was able to be established.

Adult↗

Influence of a new monomeric nonionic radiographic contrast medium (iobitridol-350 versus NaCl) on cutaneous microcirculation: single-center, prospective, randomized, double-blind phase IV study in parallel group design.

This single-center, prospective, randomized, double-blind phase IV study with parallel-group design was performed to test whether injection of a newly designed non-ionic monomeric radiographic contrast medium in the axillary artery influences the ipsilateral cutaneous microcirculation. Twenty patients with coronary heart disease or suspected coronary heart disease were investigated. Ten patients received iobitridol and 10 normal saline solution. The confirmatory target variable was the capillary erythrocyte velocity (v(RBC)). The v(RBC) was continuously recorded before and up to 3 min after the injection of iobitridol or normal saline solution and subsequently evaluated off-line. Thirty seconds after injection of 20 ml iobitridol, v(RBC) was reduced by 32% (P < 0.05). This was the strongest reduction, but v(RBC) was reduced at all time points measured up to 180 s following the injection (P < 0.05 up to 180 s). The overall reduction in v(RBC) was also statistically significant (P 0.0446). In contrast, there was a tendency toward an increase in v(RBC) following injection of 20 ml normal saline (P 0.0512). There was also a tendency toward a difference in the time course of changes in v(RBC) following injection of iobitridol compared to normal saline (P 0.0607). The decrease in v(RBC) following iobitridol injection (standardized difference (SD) according to Cohen, 0.67) can be regarded as biometrically weak, and the increase following normal saline injection (SD, 0.24) as very weak. The microcirculatory disturbance induced by iobitridol injection is less severe than that due to comparable high-viscosity contrast media.

Aged↗

Quantitative morphodynamics of endothelial cells within confluent cultures in response to fluid shear stress.

To evaluate shear stress-induced effects on cultured cells we have extended the mechanical setup of a multichannel in vitro rheological system and developed software allowing entire processing control and image data analysis. The values of cell motility, degree of orientation (alignment), and cell elongation were correlated as a function of time (morphodynamics). Collective and individual endothelial cells within confluent cultures displayed a shear stress-dependent characteristic phase behavior of the following time course: resting conditions (phase I), change of motility (phase II), onset of alignment (phase III), and finally cell elongation (phase IV). Especially cell motility was characterized by a randomized zigzag movement around mean trajectories (fluctuations) together with mean cell locomotion. Onset of shear stress caused a down-regulation of fluctuations of 30% within <10 min and simultaneously increased locomotion velocities preferring the flow direction (phase II). After a lag period of 10 to 20 min cells orientated in the direction of flow (phase III) without significant cell elongation, which finally occurs within hours (phase IV). These data provide first evidence that cells within confluent endothelial monolayers respond to shear stress with a characteristic phase behavior.

Animals↗

Influence of the onion as an essential ingredient of the Mediterranean diet on arterial blood pressure and blood fluidity.

Mediterranean diet has got a favourable effect on life expectancy. One of the crucial components of the diet are onions. In an open and a randomized, placebo-controlled, double-blind, cross-over phase-I study a spontaneous pharmacological effect 5 h after administration of an onion-olive-oil maceration capsule formulation on arterial blood pressure could be demonstrated in apparently healthy subjects. In addition to a decrease in arterial blood pressure, a significant reduction in plasma viscosity and haematocrit were observed. These results are indicating a vasodilative effect of the onion-olive-oil-maceration product. The stickiness of the platelets was reduced. The effects were stronger in subjects with reduced blood fluidity compared to those subjects with normal rheological parameters.

Adolescent↗