Biomedical subjects

M Wolzt

Publications and source records attributed to M Wolzt.

At least 73 records · Page 4Linked to original sources

PubMed1997

Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers.

BACKGROUND AND PURPOSE: There is evidence that ocular blood flow plays a critical role in the clinical course of glaucoma. Hence a reduction in ocular blood flow due to topical antiglaucoma treatment should be avoided. The purpose of this study was to characterize the effect of antiglaucoma drugs on ocular hemodynamics. METHODS: In a double-blind, placebo-controlled, randomized crossover study, we investigated the effects of single topical doses of five beta-blocking agents (befunolol, betaxolol, levobunolol, metipranolol, and timolol), two adrenergic agents (clonidine and dipivefrin [INN, dipivefrine]), and a parasympathomimetic agent (pilocarpine) on ocular and systemic hemodynamics in healthy subjects (n = 10). Fundus pulsation amplitudes in the macula and the optic disc were measured to characterize pulsatile choroidal and optic disc blood flow, respectively. Moreover, central retinal and ophthalmic artery blood flow velocities were measured by Doppler ultrasound. RESULTS: Befunolol, metipranolol, timolol, clonidine, and dipivefrin reduced fundus pulsations in the macula and the optic disc (-9% to -14% versus baseline). In contrast, betaxolol, levobunolol, and pilocarpine had no effect on fundus pulsations. Antiglaucoma drugs had no effect on either blood flow velocities in the central retinal or the ophthalmic artery or systemic hemodynamics. CONCLUSIONS: Our results indicate that befunolol, metipranolol, timolol, clonidine, and dipivefrin reduce choroidal and optic disc blood flow. This could be caused by drug diffusion to the choroid, which may cause vasoconstriction. Ocular blood flow reduction was not observed with betaxolol, levobunolol, or pilocarpine. The lack of effect of all drugs under study on central retinal blood flow velocity might partially be the result of autoregulative mechanisms. Because optic nerve head blood flow likely plays a critical role in the clinical course of glaucoma, the use of antiglaucoma drugs, which reduce blood flow, should be reconsidered.

Adrenergic Agents↗

PubMed1997

Characterization of angiotensin-II effects on cerebral and ocular circulation by noninvasive methods.

AIMS: The role of the renin-angiotensin-system (RAS) in the cerebral and ocular circulation is still a matter of controversy. In vitro and animal data lead to partially contradicting results. However, direct investigation of locally generated angiotensin II (Ang II) in humans is not possible in vivo. Hence, we hypothesised that it might be possible to characterize local effects of Ang II by comparing systemic and local haemodynamic parameters during exogenous Ang II infusion. METHODS: In a placebo-controlled, double-blind, two-way cross over study blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured during stepwise increasing doses of Ang II in 10 healthy subjects. Blood flow velocities were assessed by Doppler sonography, fundus pulsation amplitudes (FPA), which estimate local pulsatile ocular blood flow were measured by laser interferometry. Additionally, systemic blood pressure and pulse rate were measured. RESULTS: Ang II dose-dependently decreased resistive index (RI) and increased mean flow velocities (MFV) in both arteries. Fundus pulsation amplitude was dose-dependently decreased by Ang II, whereas mean arterial pressure (MAP) was significantly increased. Pulse pressure amplitude (PPA) was not affected by Ang II administration. There was a high degree of correlation between changes in RIs and the analogously calculated PPA/systolic blood pressure during Ang II infusion, which indicates that the changes in RI after Ang II administration can be attributed to changes in systemic haemodynamics. Calculation of total local ocular blood flow from fundus pulsation amplitudes and changes in flow pulsatility in the ophthalmic artery further argue against significant blood flow changes after Ang II administration. CONCLUSIONS: Interpretation of data from Doppler sonography and laser interferometry must be done very carefully when concomitant changes in systemic haemodynamics occur. RI cannot necessarily be taken as an index of distal vascular resistance in these cases and changes in MFV can be caused by changes in vessel diameter or in blood flow. Moreover, FPA cannot be taken as a measure of ocular blood flow if no additional data on flow pulsatility are available. The combination of our systemic and local haemodynamic data indicates that cerebral and ocular circulation are comparably insensitive to changes in local Ang II concentrations. Fundus pulsation and blood flow velocity measurements indicate that neither choroidal nor optic nerve head blood flow are significantly affected by administration of Ang II.

Adult↗

PubMed1997

Effects of losartan on cerebral and ocular circulation in healthy subjects.

AIMS: The introduction of specific inhibitors of AT1 receptors, such as losartan, has enabled the investigation of the renin-angiotensin-system (RAS) in humans in vivo. We studied the role of the RAS in the cerebral and ocular circulation in healthy subjects. Haemodynamic effects of orally administered losartan were investigated with non-invasive methods. METHODS: In a placebo-controlled randomized, double-blind two way crossover design losartan (100 mg orally) or placebo was administered in 10 healthy subjects. The effect of losartan was studied at hourly intervals for 8 h. In addition, the effect of losartan on haemodynamic changes induced by exogenous angiotensin II (Ang II) was assessed. Blood flow velocities in the ophthalmic and the middle cerebral artery (OA, MCA) were measured with Doppler sonography. Pulsatile choroidal blood flow was estimated with laser interferometric measurement of fundus pulsation. RESULTS: Losartan significantly increased fundus pulsation amplitude (+11%, 95% CI: 5 to 16% P<0.0001), tended to increase resistive index in the ophthalmic artery (+12%, 95% CI: 0 to 23%) and tended to decrease mean arterial pressure (-15%, 95% CI: -23 to -1%). Ang II induced effects on cerebral, ocular and systemic haemodynamics were prevented by preceding administration of losartan. CONCLUSIONS: The present data suggest that Ang II is not a major determinant of cerebral and ocular blood flow in vivo. The observed changes in cerebral and ocular haemodynamic parameters after losartan administration reflect effects on systemic blood pressure.

Adult↗

PubMed1997

Ocular and systemic reactivity to isoprenaline in patients with insulin-dependent diabetes mellitus.

There is experimental evidence of decreased beta-adrenergic myocardial sensitivity in patients with insulin-dependent diabetes mellitus (IDDM). In the present study we hypothesized that the ocular response to isoprenaline, as a consequence of increased arterial vessel rigidity, might also be blunted in patients with IDDM. We therefore compared the correlation between systemic pulse pressure amplitude (PPA) and fundus pulsation amplitude (FPA) during intravenous isoprenaline administration in 11 otherwise healthy IDDM patients and 11 healthy control subjects. Ocular fundus pulsations were measured by a recently developed laser interferometric method. Isoprenaline increased PPA in both study groups in a dose-dependent way, but the response was significantly less in IDDM patients (at 0.8 microgram min-1: +38% in control subjects, +27% in IDDM patients, P < 0.05 between groups). Moreover, a dose-dependent increase in FPA was observed, which again was more pronounced in healthy subjects (at 0.8 microgram min-1: +45% in controls, +17% in IDDM patients, P < 0.005 between groups). The regression line between PPA and FPA was very close to the 45 degrees line in healthy subjects, whereas it was significantly flattened in IDDM patients. In conclusion, linear regression between PPA and FPA during isoprenaline suggests arterial stiffening in patients with IDDM. Hence, comparison of systemic PPA and FPA during isoprenaline provocation may be a useful method of estimating changes in arterial capacitance in patients with diabetes mellitus.

Adrenergic beta-Agonists↗

PubMed1997

Cisplatin-induced renal effects and thromboxane A2 receptor blockade.

The aim of this study was to evaluate the renal protective effect of linotroban, a thromboxane A2 receptor antagonist, in 25 patients with malignant tumours scheduled for cisplatin therapy. Cisplatin was administered 1 h after the start of a 24-h continuous infusion of linotroban or placebo. Glomerular filtration rate and effective renal plasma flow were measured. Infusions of cisplatin decreased glomerular filtration rate by 17 +/- 25 mL min-1 (P = 0.049 vs. baseline) and effective renal plasma flow by 94 +/- 150 mL min-1 (P = 0.049 vs. baseline) in the placebo group. In the linotroban group a decrease in glomerular filtration rate by 11 +/- 18 mL min-1 (P = 0.050 vs. baseline) and in effective renal plasma flow by 26 +/- 63 mL min-1 (P = 0.2 vs. baseline) was noted. However, no difference was noted between groups in response to treatment. Our findings indicate that linotroban may not be useful for prevention of cisplatin's acute nephrotoxic effects.

Adult↗

PubMed1997

Nitric oxide synthase inhibition in the histamine headache model.

Histamine has been widely used experimentally to induce headache in healthy subjects and migraine in migraineurs. There is evidence that the vascular effects of histamine are at least partially mediated by nitric oxide (NO). Hence we hypothesized that subjective symptoms and hemodynamic effects of histamine could be reduced by systemic NO-synthase inhibition. We therefore studied the effect of pretreatment with N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO-synthase, or placebo on headache, flush and discomfort scores during histamine infusion. Additionally, blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured. Whereas L-NMMA blunted the effect of histamine in the ophthalmic artery and the ocular circulation, NO-synthase inhibition did not mitigate subjective symptoms. Histamine did not affect mean blood flow velocities in the middle cerebral artery. Hence, we conclude that NO-synthase inhibition reduces the histamine-induced vascular effects in the ocular circulation, but is not sufficient to attenuate or abort the subjective symptoms provoked by histamine infusion.

Adult↗

PubMed1997

Effects of changes in intraocular pressure on human ocular haemodynamics.

PURPOSE: Myogenic autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. Ocular perfusion pressure is defined as the difference between ocular arterial pressure and ocular venous pressure, the latter dependent on intraocular pressure (IOP). The aim of the present study was to investigate the effect of moderate increases in IOP on ocular haemodynamics. METHODS: Changes in IOP (+ 10 mmHg, +20 mmHg) were induced by a suction cup in 10 healthy subjects. Ocular fundus pulsations in the macula and the optic disc were measured by laser interferometry; blood flow velocities in the central retinal artery (CRA) and in the ophthalmic artery (OA) were measured by Doppler sonography. RESULTS: Changes in IOP caused a significant reduction in fundus pulsations, which was more pronounced in the macula (at +10 mmHg: -9 +/- 2%, p < 0.01; at +20 mmHg: -19 +/- 3%, p < 0.001) than in the optic disc (at +10 mmHg: -5 +/- 2% (ns); at +20 mmHg: -9 +/- 3%, p < 0.01). Mean flow velocity in the CRA was reduced by -5 +/- 3% at +10 mmHg (ns) and by -14 +/- 5% at +20 mmHg (p < 0.005), resistive index was increased by +4 +/- 1% at +10 mmHg (p < 0.05) and by +6 +/- 2% at +20 mmHg (p < 0.01). In contrast, a rise in IOP did not affect blood flow parameters in the OA. CONCLUSIONS: Our results from fundus pulsation measurements indicate that choroidal blood flow decreases when IOP is increased. The Doppler sonographic findings in the CRA indicate reduced blood flow velocity in this artery during raised IOP.

Adult↗

PubMed1997

Effects of endothelin-1 (ET-1) on ocular hemodynamics.

PURPOSE: There is evidence from in vitro and animal data that endothelin-1 (ET-1) plays an important role in ocular blood flow. The aim of the present study was to investigate the effect of systemic ET-1 administration on ocular circulation in healthy subjects. METHODS: In a double blind, placebo-controlled, randomized, 2-way cross over study in 10 healthy male subjects, we administered stepwise, increasing doses of ET-1 (0 (saline), 1.25, 2.5 and 5.0 ng/kg/minutes; 20 minutes per dose (level) or placebo. Blood flow velocity in the ophthalmic artery as well as ocular fundus pulsations in the macula and the optic disc, and systemic hemodynamic parameters were measured. RESULTS: ET-1 dose-dependently reduced fundus pulsations in the macula (maximum effect -12 +/- 2% versus baseline; p < 0.001 versus baseline and placebo) and the optic disc (maximum effect: -19 +/- 5% versus baseline; p < 0.001 versus baseline and placebo), but did not affect blood flow velocity in the ophthalmic artery or systemic hemodynamics. CONCLUSIONS: Endothelin-1 reduces pulsatile blood flow in the choroid and the optic disc at doses which do not affect systemic hemodynamics or flow velocity in the ophthalmic artery. These results indicate that ocular circulation is particularly sensitive to changes in local ET-1 concentration and confirms the hypothesis that ET-1 may play a role in ocular vascular diseases.

Adult↗

PubMed1997

Reproducibility and sensitivity of scanning laser Doppler flowmetry during graded changes in PO2.

AIMS/BACKGROUND: Recently a commercially available scanning laser Doppler flowmeter has been produced, which provides two dimensional maps of the retinal perfusion. The aim of the present study was to investigate the reproducibility and the sensitivity of these measurements. METHODS: 16 healthy subjects were randomised to inhale different gas mixtures of oxygen and nitrogen in a double blind crossover study. The following gas mixtures of oxygen and nitrogen were administered: 100% oxygen + 0% nitrogen, 80% oxygen + 20% nitrogen, 60% oxygen + 40% nitrogen, 40% oxygen + 60% nitrogen, 30% oxygen + 70% nitrogen, 20% oxygen + 80% nitrogen, 15% oxygen + 85% nitrogen, and 10% oxygen + 90% nitrogen. Retinal haemodynamic variables and systemic haemodynamics were measured during all inhalation periods. Recordings under resting conditions were performed three times to calculate intraclass coefficients. RESULTS: In two subjects we did not obtain technically adequate results. A dose dependent change in retinal blood flow during graded oxygen breathing was observed (p < 0.001). During 100% oxygen breathing blood flow decrease was between 29% and 33%, whereas blood flow increase was between 28% and 33% during inhalation of 10% oxygen + 90% nitrogen. CONCLUSIONS: Scanning laser Doppler flowmetry has an acceptable reproducibility and is appropriate for description of the effect of graded changes in PO2 on retinal haemodynamics. The main problems with the system are the large zero offset, the fixation during retinal scanning, and the neglect of blood flow changes during the cardiac cycle.

Adult↗

PubMed1997

Exhaled NO during graded changes in inhaled oxygen in man.

BACKGROUND: Nitric oxide (NO) is present in the exhaled air of animals and humans. In isolated animal lungs the amount of exhaled NO is decreased during hypoxia. A study was undertaken to determine whether changes in arterial oxygen tension affect levels of exhaled NO in humans. METHODS: Sixteen healthy subjects were randomised to inhale different gas mixtures of oxygen and nitrogen in a double blind crossover study. Eight gas mixtures of oxygen and nitrogen (fractional inspired oxygen concentration (FiO2) 0.1 to 1.0) were administered. Exhaled NO was measured with a chemiluminescence detector from end expiratory single breath exhalation. RESULTS: A dose-dependent change in exhaled NO during graded oxygen breathing was observed (p = 0.0012). The mean (SE) exhaled NO concentration was 31 (3) ppb at baseline, 39 (4) ppb at an FiO2 of 1.0, and 26 (3) ppb at an FiO2 of 0.1. CONCLUSIONS: The NO concentration in exhaled air in healthy humans is dependent on oxygen tension. Hyperoxia increases the level of exhaled NO, which indicates increased NO production. The mechanism behind this phenomenon remains to be elucidated.

Administration, Inhalation↗

PubMed1997

Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans.

It is well known that changes in PCO2 or PO2 strongly influence cerebral and ocular blood flow. However, the mediators of these changes have not yet been completely identified. There is evidence from animal studies that NO may play a role in hypercapnia-induced vasodilation and that NO synthase inhibition modulates the response to hyperoxia in the choroid. Hence we have studied the effect of NO synthase inhibition by NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 micrograms.kg-1.min-1) on the changes of cerebral and ocular hemodynamic parameters elicited by hypercapnia and hyperoxia in healthy young subjects. Mean flow velocities in the middle cerebral artery and the ophthalmic artery were measured with Doppler ultrasound, and ocular fundus pulsation amplitude, which estimates pulsatile choroidal blood flow, was measured with laser interferometry Administration of L-NMMA reduced ocular fundus pulsation. (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia (PCO2 = 48 mmHg) significantly increased mean flow velocities in the middle cerebral artery (+26%, P < 0.01) and fundus pulsation amplitude (+16%, P < 0.005) but did not change mean flow velocity in the ophthalmic artery. The response to hypercapnia in the middle cerebral artery (P < 0.05) and in the choroid (P < 0.05) was significantly blunted by L-NMMA. On the contrary, L-NMMA did not affect hyperoxia-induced (PO2 = 530 mmHg) hemodynamic changes. The hemodynamic effects of L-NMMA (at baseline and during hypercapnia) were reversed by coadministration of L-arginine. The present study supports the concept that NO has a role in hypercapnia induced vasodilation in humans.

Adult↗

PubMed1997

Effect of nitric oxide synthase inhibition on renal hemodynamics in humans: reversal by L-arginine.

Animal experiments indicate that inhibition of nitric oxide synthase (NOS) influences renal hemodynamics and that this effect can be reversed by L-arginine, the precursor of NO synthesis. We have therefore studied the effects of an inhibitor of NOS, N(G)-monomethyl-L-arginine (L-NMMA), and a subsequent coinfusion with L-arginine on renal hemodynamics. In a double-blind, randomized crossover design, eight healthy volunteers (means +/- 1SD, 25.6 +/- 3.1 yr) received a primed constant infusion of L-NMMA (3 mg/kg bolus infusion over 5 min, followed by 50 microg x kg(-1) x min(-1) over 120 min) with subsequent coinfusion of L-arginine (17 mg x kg(-1) x min(-1) over 30 min). In the absence of a hypertensive response, L-NMMA decreased renal plasma flow to 79% of baseline (P < 0.005); this effect was abrogated by L-arginine. Glomerular filtration rate was not affected, NO exhalation was reduced to 30% of baseline (P < 0.005) by L-NMMA, and this effect was attenuated by L-arginine. Our results demonstrate that basal NO production maintains renal blood flow in vivo in humans. In addition, the renal vasculature is particularly sensitive to inhibition of NOS, and these pharmacodynamic effects can be reversed by excess doses of L-arginine.

Adult↗

PubMed1997

Hemodynamic effects of parathyroid hormone-related peptide-(1-34) in humans.

It has been suggested that PTH-related peptide-(1-34) (PTHrP) is a regulator or modulator of regional or systemic cardiovascular function with varying vasodilating actions in different species. We have studied the cardiovascular pharmacodynamic profile of PTHrP in healthy humans. In a double blind, placebo-controlled, cross-over study design, eight healthy subjects were assigned to stepwise increased i.v. doses of PTHrP. In addition, a dose-response curve to PTHrP was constructed in a dorsal hand vein in eight subjects. PTHrP dose-dependently increased pulse rate and renal plasma flow by more than 50% (P < 0.0001 for both parameters, by ANOVA), but only a small venodilating response was seen in hand vein experiments, and no effect was noted on mean arterial blood pressure or cardiac inotropic performance. Although it is unlikely that PTHrP regulates systemic hemodynamics, its chronotropic effect and its potent action on renal plasma flow may represent the primary cardiovascular physiological targets of action.

Adult↗

PubMed1997

Renal and ocular hemodynamic effects of insulin.

There is evidence that the vasodilator action of insulin is mediated by the release of nitric oxide (NO). We hypothesized that euglycemic hyperinsulinemia might increase renal and ocular blood flow, and that the vasodilator capacity of insulin might be NO-dependent. Euglycemic insulin clamps were performed in 10 healthy subjects. Sixty minutes after the start of insulin administration, an intravenous coinfusion of N-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, or of norepinephrine (NE), an endothelium-independent vasoconstrictor, was started. Renal plasma flow was measured by para-aminohippurate (PAH) clearance method. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. Renal plasma flow and ocular fundus pulsations were increased by insulin. L-NMMA almost completely abolished the vasodilative effects of insulin, whereas the effects of combined infusion of insulin and NE were approximately the sum of the hemodynamic changes induced by each agent alone. The results show that during euglycemic hyperinsulinemia, renal and ocular blood flow are increased, which may be mediated either by a local vasodilator effect or a systemic increase in flow. The hemodynamic effects of insulin in the kidney and the eye are at least partially dependent on NO synthesis. Because the insulin plasma levels we obtained are in the high physiological range, it may be assumed that insulin plays a role in renal and ocular blood flow regulation.

Adult↗

PubMed1997

Nitric oxide and ocular blood flow in patients with IDDM.

Endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disorders such as diabetic retinopathy. We hypothesized that either local endogenous nitric oxide (NO) synthesis or local reactivity to endogenous NO might be impaired in patients with IDDM and that this may contribute to the development of diabetic retinopathy. Ten otherwise healthy patients with long-standing IDDM and ten healthy control subjects were studied according to an open randomized two-way cross-over design. Subjects received intravenous infusions of either N(G)-monomethyl-L-arginine, an inhibitor of NO-synthase, or L-arginine, the precursor of NO synthesis, on two separate study days. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine decreased fundus pulsations and blood flow velocity in the ophthalmic artery and increased blood pressure in healthy subjects. The responses to NO-synthase inhibition were significantly less in diabetic subjects. In contrast, L-arginine caused a comparable increase in fundus pulsations and decrease in blood pressure in both cohorts. These results indicate that systemic and ocular hemodynamic reactivity to NO-synthase inhibition is reduced in patients with long-standing IDDM, compared with healthy control subjects. Thus, this study indicates that either NO-synthase activity is increased or NO sensitivity is decreased in patients with IDDM and supports the concept of an involvement of the L-arginine-NO system in the pathophysiology of diabetic retinopathy.

Adult↗

PubMed1997

Thromboxane A2 does not mediate angiotensin II-dependent nonischemic peripheral vasoconstriction in healthy men: a pilot study.

It has been suggested that angiotensin II-dependent hemodynamic effects are in part mediated by thromboxane A2 (TXA2). The present study investigates in 6 healthy normotensive men whether prostaglandin H2-TXA2 receptor blockade with 100 mg of linotroban (5(2-(phenylsulfonylamino)ethyl)-thienyloxy-acetic acid) p.o. influences angiotensin II-dependent peripheral regional vasoconstriction. Moreover, the regional balance of thromboxane B2 (TXB2), a stable metabolite of TXA2, across the leg vascular bed was assessed at baseline conditions as well as during exogenous infusion (0.2 microgram/min) of angiotensin II. Net transfemoral TXB2 balance was calculated from the respective arteriovenous plasma concentration differences and the corresponding regional plasma flow, the latter being determined by indocyanine-green dye, using appropriate catheterization techniques. Angiotensin II (0.2 microgram/min) induced a 66% increase in leg vascular resistance (p < 0.01) without affecting systemic hemodynamics. These regional hemodynamic effects of angiotensin II were not influenced by prostaglandin H2-TXA2 receptor blockade. Baseline TXB2 balance across the femoral vascular bed was equilibrated at slight extraction rates or around zero and remained unchanged during angiotensin II infusion. These results suggest that, in healthy man, angiotensin II-dependent, nonischemic peripheral vasoconstriction is not mediated by TXA2. Possible benefits of prostaglandin H2-TXA2 receptor blockade in pathological conditions with tissue malperfusion or ischemia are discussed.

Adult↗

PubMed1997

Comparison of the effects of different low molecular weight heparins on the hemostatic system activation in vivo in man.

In a double-blind, randomized, cross-over study the effects of single subcutaneous doses of 120 anti-Xa units/kg body wt. of three different low molecular weight heparin (LMWH) preparations were investigated in 15 healthy subjects by determination of thrombin-antithrombin III complex (TAT), prothrombin fragment 1.2 (f1.2), and beta-thromboglobin (beta-TG) in shed blood and in venous blood. Certoparin, dalteparin, and enoxaparin significantly inhibited coagulation activation marker formation in shed blood. The substantial inhibition of TAT and f1.2 formation was slightly more pronounced in response to certoparin. beta-TG was decreased following certoparin and enoxaparin, but not following dalteparin. However, no difference between groups was detectable. A small but consistent decrease of f1.2 formation in venous blood was noted for all LMWHs and dalteparin and enoxaparin, but not certoparin, inhibited TAT formation. Only a minor impact of the three LMWH preparations was noted on beta-TG plasma concentrations. Our data indicate that the studied LMWH preparations have a major impact on blood clotting in the activated state and inhibit in vivo the hemostatic system to a comparable extent.

Adult↗

PubMed1996

The effect of inhalation of different mixtures of O2 and CO2 on ocular fundus pulsations.

The effect of different mixtures of O2 and CO2 on pulsatile ocular blood flow as assessed by laserinterferometric measurement of fundus pulsations was studied. This was done in an effort to identify the gas mixture with an optimal O2/CO2 ratio for treatment in central retinal artery occlusion (CRAO). In a double-blind, randomized, placebo-controlled, six-way cross-over study, 20 healthy young subjects were studied. Fundus pulsation amplitude in the macula (FPAM) and in the optic disc (FPAO), arterialized capillary blood gases, and systemic haemodynamics were measured during baseline and 12 min inhalation periods of 100% O2, mixtures of 2.5%, 5%, 8%, 10% CO2 with oxygen, and air as placebo. The FPAM and FPAO decreased at 100% oxygen (FPAM: -6.2%, P < 0.01; FPAO: -15.1%. P < 0.001), but dose dependently increased with addition of CO2: whereas FPAM was not different versus placebo during inhalation of 2.5% CO2 with oxygen (+0.3%), addition of 5% CO2 and 8% CO2 to oxygen significantly increased FPAM versus placebo (+10.6%, P < 0.01 and +25.9%, P < 0.001, respectively), FPAO was slightly decreased by addition of 2.5% CO2 to oxygen (-2.6%, P < 0.05 versus placebo), 5% CO2 neutralized oxygen's effects on FPAO (+1.5%) and 8% CO2 + 92% O2 significantly increased FPAO (+16.0%, P < 0.001 versus placebo). Inhalation of 90% O2 + 10% CO2 was not tolerated by 19 subjects. Administration of 5% and 8% CO2 with oxygen significantly increased mean arterial pressure. We conclude that addition of 5% CO2 to oxygen is appropriate to maintain or even increase pulsatile ocular blood flow in the macula and optic disc at a level comparable to air-breathing. Addition of higher percentages of CO2 further increases fundus pulsations, with a very steep dose response relationship. Addition of 8% CO2 seems not applicable in patients due to pronounced systemic effects. Hence mixtures of 6 or 7% CO2 with oxygen should be used for further studies in patients with central retinal artery occlusion (CRAO).

Adult↗