Comment on composite-particle decay and the e+e- puzzle.
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Journal Article↗
Biomedical subjects
W Koenig
Publications and source records attributed to W Koenig.
The possible role of hemorheology in atherothrombogenesis.
Conventional risk factors predict only about 30-50% of incidental cases in cardiovascular diseases, which are still the leading cause of death in western societies. During the last decade, the importance of thrombosis as an essential mechanism in acute myocardial infarction (AMI) and stroke has been established. The introduction of thrombolysis has led to an impressive reduction in AMI case fatality and possibly also to a substantial amelioration of its prognosis. Evidence from experimental, clinical and epidemiological studies suggest, that several hemostatic and hemorheological factors (e.g., fibrinogen, Factor VII, plasma viscosity, hematocrit, red blood cell aggregation, total white cell count) might not only play an important role in the evolution of acute thrombotic events, but may also take part in the pathophysiology of atherosclerosis. An increasing number of studies reports altered hemostatic and hemorheological parameters to be associated with smoking, hyperlipoproteinemia, and high blood pressure, as well as with adverse dietary habits and other life-style factors. To date, their way of interaction with the atherosclerotic process is poorly understood. Hemorheological or hemostatic mechanisms that might promote thromboatherogenesis include the predisposition to thrombosis via a hypercoagulable state, the enhancement of atherosclerosis by fibrinogen and its metabolites, and finally the reduction of blood flow through various rheological effects (e.g., increase in plasma viscosity and red cell aggregation, or leukocyte activation). Future research should focus in more detail on the interrelationship between accepted risk factors and the hemostatic system as well as hemorheological parameters. Deeper insight into the mechanisms involved might lead to new preventive strategies as well as to therapeutic procedures in the management of atherosclerosis and associated thrombotic events.
Arteriosclerosis↗
Association between rheology and components of lipoproteins in human blood. Results from the MONICA project.
BACKGROUND: Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies. METHODS AND RESULTS: We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin. CONCLUSIONS: We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.
Adult↗
Plasma viscosity as a cardiovascular risk factor.
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Blood Viscosity↗
Blood rheology after LDL apheresis using dextran sulfate cellulose absorption--a case report.
The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia.
Adsorption↗
Lovastatin alters blood rheology in primary hyperlipoproteinemia: dependence on lipoprotein(a)?
As part of a randomized, single-blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemorheologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and deformability, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (less than or equal to 25 mg/dL) high-density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp(a) levels (greater than 25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low-density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated.
Bezafibrate↗
Comparison of once daily felodipine 10 mg ER and hydrochlorothiazide 25 mg in the treatment of mild to moderate hypertension.
The efficacy of extended release felodipine 10 mg (ER) o.d., a new dihydropyridine calcium antagonist, and 25 mg hydrochlorothiazide (HCTZ) o.d. have been compared in a randomized, double-blind, crossover trial in 28 mildly to moderately hypertensive subjects (supine diastolic blood pressure, BP, greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg on three separate occasions). Both drugs significantly reduced systolic and diastolic BP in the sitting position felodipine from 157.1/93.8 mm Hg at baseline to 133/78.9 mm Hg 2.5 h after medication and to 138/82.7 mm Hg after 2 weeks of treatment, and HCTZ from 156/95.6 mm Hg to 147/88.4 mm Hg 2.5 h after medication and to 149/89.5 mm Hg also after 2 weeks. A decrease of the same magnitude in standing systolic and diastolic BP was observed after both treatment regimens with the exception of diastolic BP 2.5 h after dosing with HCTZ, which was not significantly lower. At all times (2.5 h and 2 weeks), the reduction in systolic and diastolic BP was greater after felodipine compared to HCTZ. Heart rate was significantly increased after felodipine in both the sitting and standing positions, and both 2.5 h following medication and after 2 weeks of treatment. The difference between the regimens was significant only 2.5 h after dosing. Overall, felodipine 10 mg ER o.d. was superior to 25 mg HCTZ o.d. in lowering BP.
Administration, Oral↗
Association between plasma viscosity and blood pressure. Results from the MONICA-project Augsburg.
The relationship between determinants of blood viscosity and blood pressure (BP) variables was studied in a large sample of a population aged 25 to 64 years. Plasma viscosity, hemoglobin, and total serum protein were examined. Systolic and diastolic BP and the prevalence of hypertension showed a crude positive association with plasma viscosity levels in both sexes. Age, body mass index, and total serum protein appeared to have a confounding effect on this relationship, whereas hemoglobin, smoking behavior, and alcohol consumption did not. A crude positive association was also found between total serum protein levels and the prevalence of hypertension in men and women; however, since total serum protein was treated as a covariable, no further analyses were carried out. In contrast to findings reported in the literature, hemoglobin levels were not correlated with BP variables in either sex. After adjusting for all confounders, a significant main effect of plasma viscosity still was found. However, the magnitude of the effect was not as large as for body mass index, a well-established risk variable for hypertension. These results indicate that BP is positively associated with plasma viscosity. Whether increased plasma viscosity in hypertension constitutes a primary or a secondary phenomenon remains to be answered. Since plasma viscosity is significantly associated with hypertension but any BP variable, increased levels of plasma proteins (particularly fibrinogen as the main determinant of plasma viscosity) may represent the cause for elevated plasma viscosity. This might contribute to persistently increased resistance to blood flow on the microcirculatory level in arterial hypertension.
Adult↗
Catecholamines and the renin-angiotensin-aldosterone system during treatment with felodipine ER or hydrochlorothiazide in essential hypertension.
The neurohumoral responses after 10 mg of felodipine extended release (ER), a new dihydropyridine calcium antagonist, and 25 mg of hydrochlorothiazide (HCTZ) were compared in a randomized, double-blind, crossover trial in 28 mild to moderate hypertensives. Antihypertensive drugs were gradually discontinued. Felodipine ER, 10 mg was given once daily for 2 weeks; after another washout period of 1 week, patients were switched to 25 mg of HCTZ once daily and vice versa. Blood pressure (BP) was measured at baseline, 2.5 h after medication, and after 2 weeks of treatment (24 h postdosing) using an oscillometric device. Felodipine ER and HCTZ both lowered BP effectively. However, felodipine ER was superior in reducing systolic and diastolic BP during the short term and medium term. Treatment with felodipine ER over 2 weeks increased sympathetic outflow as indicated by elevated plasma norepinephrine levels, whereas plasma epinephrine was mainly unaffected, as were plasma renin and aldosterone levels. On the other hand, 25 mg of HCTZ increased plasma renin and aldosterone, but left catecholamines unchanged. Despite persistent increased sympathetic activity, the reduction in BP in this study was more pronounced after felodipine ER as compared to HCTZ. The lack of a difference between heart rates under both medications after 2 weeks of treatment suggests a resetting of the baroreflex by felodipine ER and furthermore that the increased norepinephrine levels may not be clinically relevant, but demonstrate the maintained baroreflex activity. HCTZ, in doses as low as 25 mg, is still capable of stimulating the renin-angiotensin-aldosterone system.
Adult↗
Left ventricular function and wall thickness in long-term insulin-dependent diabetes mellitus: an echocardiographic study.
Left ventricular function and wall thickness were evaluated in 111 type I diabetic subjects (mean age 25.5 +/- 9 years, mean duration of diabetes 13.4 +/- 6.2 years), using 2-D-derived M-mode echocardiography. Patients were carefully selected for the absence of major coronary risk factors or manifest cardiac disorders, and compared with 91 age- and sex-matched control subjects. Fractional shortening and the maximal velocity of cirumferential fibre shortening did not differ significantly between the two groups. Furthermore, no differences were found in the diastolic functional parameter of velocity of circumferential fibre extension. Posterior wall thickness was significantly increased in the diabetic patients compared to the controls (9.5 +/- 1.8 mm vs. 8.4 +/- 1.3 mm. P less than 0.01). As the thickness of the interventricular septum was also moderately increased (9.2 +/- 2.2 mm vs. 8.9 +/- 1.7 mm, NS), these findings provide evidence for an early structural change of the myocardium in young diabetic patients without clinically relevant functional consequences.
Adult↗
Effects of felodipine ER and hydrochlorothiazide on blood rheology in essential hypertension--a randomized, double-blind, crossover study.
The haemorheological effects of felodipine extended release (ER), a new dihydropyridine calcium antagonist, were compared with hydrochlorothiazide (HCTZ) in 28 mild to moderate hypertensives (18 men and 10 women, aged 30-70 years) in a randomized, double-blind, crossover trial. Antihypertensive drugs were gradually discontinued. Felodipine Er, 10 mg, was given once daily for 2 weeks, and after another wash-out period of 1 week, patients were switched to 25 mg HCTZ, once daily, and vice versa. Whole blood viscosity (BV) at three different shear stresses, haematocrit (Hct), plasma viscosity (PV), red blood cell (RBC) aggregation, RBC deformability, and fibrinogen were measured under standardized conditions 2.5 h after medication, and after 2 week of treatment (24 h post-dosing). Felodipine ER improved BV acutely, but not during treatment over a 2-week period. By contrast, HCTZ did not affect BV, but decreased RBC deformability 2.5 h after medication intake. After 2 weeks of treatment, the negative effect on RBC deformability had increased slightly. Furthermore, fibrinogen and PV were significantly elevated at this stage. In summary, felodipine ER did not improve blood rheology over a 2-week treatment period in this study. HCTZ exhibited marginal but significant negative effects on fibrinogen, PV and indices of RBC deformability, but not on RBC aggregation.
Adult↗
Effect of angiotensin-converting enzyme inhibition on human tissue renin.
This investigation was performed to assess the effect of treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril, on human tissue renin levels. A total of 41 patients were studied (32 males and 9 females, aged 48-71 years). Twenty-two of these patients received up to 5 days treatment with the ACE inhibitor ramipril (5 mg p.o.) prior to surgery, the remaining 19 patients served as controls (no ramipril treatment). Under surgery vascular tissues were removed and renin-like activities measured in carotid and renal arteries. Plasma renin and ACE activity were determined before and after surgical intervention. Vascular renin values were two- to threefold higher in ACE-treated hypertensive patients compared to normotensive and untreated hypertensive controls (irrespective of concomitant atherosclerotic lesions). There were no differences in vascular renin observed between primary (essential) and secondary hypertension. In the hypertensive patients treated with ramipril, blood pressures were markedly (but not significantly) lowered in 12 patients. A similar pattern was observed for treatment-induced changes in plasma renin (increased) and ACE activity (decreased). The findings of this study demonstrate that treatment with an ACE inhibitor, such as ramipril, evokes changes in extrarenal tissues similar to those demonstrable in plasma. Conceivably, the blood pressure-lowering effect of ACE inhibition on human tissue is partially induced at the vascular level.
Aged↗
Neurological outcome after a severe herpes simplex encephalitis treated with acyclovir and beta-interferon. Time course of intracranial pressure.
A severe herpes simplex encephalitis with documented intra-cerebral lesions and brain edema was treated successfully with acyclovir and beta-interferon. The increase in intracranial pressure during the second week was well controlled by ICP monitoring. Life-threatening pressure peaks were avoided through the use of thiopental, osmodiuretics, TRIS, and lidocaine.
Acyclovir↗
Hemodynamic effects of alinidine (ST 567) at rest and during exercise in patients with chronic congestive heart failure.
Selective inhibition of sinus node function offers the possibility to decrease heart rate and reduce myocardial oxygen consumption in patients with impaired cardiac function, if myocardial contractility is not further attenuated. To study the influence of a specific sinus node inhibitor on myocardial function, alinidine was given to 10 patients with chronic congestive heart failure and stable sinus rhythm. Radionuclide ventriculography was used to monitor left ventricular function at rest and during a standardized exercise protocol. After a bolus injection of 45 mg of alinidine followed by infusion of 10 mg/hr, radionuclide studies were repeated 1.5 and 3 hours later. The results show that left ventricular ejection fraction, stroke volume, and end-diastolic volume index were essentially unchanged, whereas cardiac index decreased by 10% at rest and during exercise. Heart rate decreased markedly by 14% at rest and by 13% during exercise. Systolic blood pressure was reduced by 6% at rest and by 14% during exercise. As a result of the marked decrease of these two parameters, a pronounced effect was seen on rate-pressure product with a 19% decrease at rest and a 24% decrease during exercise. No significant side effects were observed. Alinidine might be given to patients with chronic congestive heart failure and sinus rhythm in doses up to 45 mg without exerting a clinically relevant negative inotropic effect. Therefore it may represent an alternative to other drugs when a decrease in heart rate is desired to reduce myocardial oxygen consumption.
Aged↗
The effects of calcium channel blockers on blood fluidity.
Although vasodilation, direct cardiac actions, or both represent the main properties of calcium channel blockers, there are further pharmacologic effects that may be therapeutically relevant. For example, hemorrheological effects, which have been demonstrated for a variety of calcium antagonists, have received relatively little attention to date. Hemorrheology describes the mechanics of blood and its components. It is of particular interest in the context of cardiovascular disease, as it has been shown that under certain conditions (reduced pump function, impaired vasomotor reserve), parameters of blood fluidity may be crucial for tissue perfusion. Whole-blood viscosity is the dominating factor in large arteries. For geometrical reasons, plasma viscosity and the rheological properties of blood cells may become of paramount importance at the microcirculatory level. In ischemic states, erythrocytes may be depleted of ATP, which they need for maintenance of normal shape and for transformation. This results in rigidification of the red blood cell and hindrance of its passage in the microcirculatory bed. Hence, blood flow deteriorates with the consequence of further unfavorable changes of the "milieu interieur," leading to the induction of a vicious cycle. Although effects on several hemorrheological parameters, for example, whole-blood viscosity, plasma viscosity, and red cell aggregation, can be demonstrated for various calcium channel blockers, the main rheological effects of these compounds are believed to consist in the improvement of erythrocyte deformability. When the ATP-dependent calcium pump is impaired in ischemia, calcium channel blockers may inhibit the slow inward transmembrane calcium flux and prevent the accumulation of intracellular calcium.
Blood Viscosity↗
Is increased plasma viscosity a risk factor for high blood pressure?
Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two-stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty-four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cholesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and demonstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be answered from cross-sectional data. However, even if plasma hyperviscosity represents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account.
Adult↗
Morbidity and mortality of myocardial infarction in the MONICA study area Augsburg in 1985.
In the year 1985, 998 (734 men, 264 women) cases of acute coronary events were registered among the 25-74 year-old residents of the study area (151,489 men and 171,093 women) of whom 583 (403 men, 180 women) died within 28 days (case fatality). Both AMI as a clinical diagnosis and AMI as a cause of death are validated by defined MONICA diagnostic criteria (acute symptoms, enzyme level, ECG, autopsy diagnosis). The AMI-risk (MONICA diagnostic categories 1, 2, 3, 9) in the study area Augsburg is relatively low (incidence: men 302, women 113; attack rate: men 444, women 138; death rate: men 241, women 92; all per 100,000 for each group). The 28-day case fatality is comparatively high (men 54%, women 67%). A comparison of the Augsburg rates with those of three other centers shows that the Augsburg figures are in the lower range.
Adult↗