Biomedical subjects

L Schmetterer

Publications and source records attributed to L Schmetterer.

At least 91 records · Page 5Linked to original sources

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

Partial blockade of nitric oxide synthase blunts the exercise-induced increase of von Willebrand factor antigen and of factor VIII in man.

BACKGROUND: Until now the effects of beta-adrenergic agonists have largely been ascribed to their ability to induce intracellular formation of cyclic adenosine monophosphate. Recently evidence has been accumulating that at least some beta1 and beta2-adrenoceptor effects may be mediated by nitric oxide (NO). Based on these studies, we hypothesized that the beta-adrenoceptor mediated increase of von Willebrand factor and factor VIII-activity (FVIII:C) in plasma during exercise, is caused by an NO-dependent mechanism. METHODS: Thirteen young healthy subjects finished an exhaustive bicycle exercise protocol while they were infused placebo or the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) on two separate days in a randomized, double blind cross-over design. FINDINGS: During exercise systemic haemodynamic changes were parallel in both treatment periods, but L-NMMA caused a partial inhibition of NO-synthase as evidenced by a 30% decrease in exhaled NO. The workload capacities were not different during L-NMMA or placebo infusion. However, under placebo treatment exercise increased vWF-Ag by a maximum of 61% (CI: 43-84; p = 0.002) and FVIII:C by 44% (CI: 31-59; p = 0.001), which was significantly attenuated when subjects were treated with L-NMMA (p <0.05): under L-NMMA treatment vWF-Ag increased by only 25% (CI: 5-51; p = 0.001) and FVIII:C by 12% (CI: 6-39; p = 0.001). INTERPRETATION: Partial blockade of NO-synthase with L-NMMA blunts the exercise-induced increase in vWF-Ag and FVIII:C. Our trial points to a role of endogenous NO-generation in the beta2-adrenergic increase in vWF/FVIII. Thus, we propose that physiologic processes which are induced by systemic beta2-adrenoceptor stimulation may at least partly be mediated by NO.

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↗

PubMed1996

A randomized, placebo-controlled, double-blind crossover study of the effect of pentoxifylline on ocular fundus pulsations.

PURPOSE: To estimate the short-term effects of pentoxifylline on ocular blood flow in healthy volunteers. METHODS: In ten healthy subjects, either 200 or 400 mg of pentoxifylline or placebo was administered intravenously over 90 minutes in a randomized, double-blind, placebo-controlled, three-way crossover study design. Noninvasive measurements of blood pressure, pulse rate, flow variables in the radial artery, ocular fundus pulsations, and whole blood viscosity and filterability were performed at baseline and at 30-minute intervals until four hours after the start of drug infusion. Ocular fundus pulsation amplitude, which has been shown to estimate the pulsatile component of the ocular blood flow, was recorded with a laser interferometer in the macula, the optic disk, and a peripheral region. RESULTS: Fundus pulsation amplitude significantly increased after infusion of pentoxifylline, with maximum effect 150 to 180 minutes after the start of the infusion. This effect was dose-dependent and more pronounced in the macula (+17%, P < .001 vs baseline, after 200 mg; and +27%, P < .001 vs baseline, after 400 mg of pentoxifylline) and the peripheral region (+14%, P < .001; and +26%, P < .001) than in the optic disk (+11%, P < .002; and +13%, P < .001). Viscosity but not filterability of whole blood dose-dependently decreased. Peak systolic flow velocity in the radial artery decreased after infusion of 400 mg of pentoxifylline. Blood pressure and pulse rate were unchanged during the observation period. CONCLUSIONS: These findings demonstrate that pentoxifylline increases pulsatile ocular blood flow in healthy volunteers. Our results support the possibility that pentoxifylline could be used therapeutically in several eye diseases, such as diabetic retinopathy.

Adult↗

PubMed1996

Cerebral and ocular hemodynamic effects of sumatriptan in the nitroglycerin headache model.

BACKGROUND AND PURPOSE: Sumatriptan is a selective 5-hydroxytryptamine1d (5-HT1d)-receptor agonist, highly effective in the short-term treatment of migraine headaches. However, the mechanism underlying the action of sumatriptan is not yet completely understood. To further characterize the vascular effects of sumatriptan, we studied the effects on cerebral and ocular circulation in the well-established nitroglycerin headache model. METHODS: In a double-blind, placebo-controlled, randomized, two-way crossover study in 10 healthy male subjects, we administered either placebo plus nitroglycerin or sumatriptan plus nitroglycerin. Blood flow velocity in the middle cerebral artery and the ophthalmic artery, as well as ocular fundus pulsations and systemic hemodynamic parameters, were measured after sumatriptan and placebo and during the following infusion of nitroglycerin. RESULTS: After infusion of nitroglycerin, blood flow velocity in the middle cerebral decreased by -13.3% versus baseline after placebo pretreatment, but by only -2.2% after sumatriptan (treatment effect, +10.8%; p < 0.05). In contrast, sumatriptan had no effect in the ophthalmic artery. Ocular fundus pulsations, which estimate local pulsatile ocular blood flow, were slightly reduced after sumatriptan. Moreover, sumatriptan partially prevented the increase in fundus pulsations during nitroglycerin infusion (treatment effect, -5.4%; p < 0.05). CONCLUSIONS: Sumatriptan prevents the effect of nitroglycerin-induced vasodilation in the middle cerebral artery but not in the ophthalmic artery, which strongly supports the concept that sumatriptan directly vasoconstricts distended basal cerebral arteries. Measurement of ocular fundus pulsations indicates that sumatriptan also has a small vasoconstrictor action on resistance vessels.

Adult↗

PubMed1996

Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers.

AIMS/BACKGROUND: Recently a laser interferometric method for topical measurement of fundus pulsations has been developed. Fundus pulsations in the macular region are caused by the inflow and outflow of blood into the choroid. The purpose of this work was to study the influence of a peripheral vasoconstricting (the alpha 1 adrenoceptor agonist phenylephrine), a predominantly positive inotropic (the non-specific beta adrenoceptor agonist isoproterenol), and a non-specific vasodilating (sodium nitroprusside) model drug on ocular fundus pulsations to determine reproducibility and sensitivity of the method. METHODS: In a double masked randomised crossover study the drugs were administered in stepwise increasing doses to 10 male and nine female healthy volunteers. Systemic haemodynamic variables and fundus pulsations were measured at all infusion steps. RESULTS: Fundus pulsation increased during infusion of isoproterenol with statistical significance versus baseline at the lowest dose of 0.1 microgram/min. Neither peripheral vasoconstriction nor peripheral vasodilatation affected the ocular fundus pulsations. CONCLUSIONS: Measurements of fundus pulsations is a highly reproducible method in healthy subjects with low ametropy. Changes of local pulsatile ocular blood flow were detectable with our method following the infusion of isoproterenol. As systemic pharmacological vasodilatation or vasoconstriction did not change fundus pulsations, further experimental work has to be done to evaluate the sensitivity of the laser interferometric fundus pulsation measurement in various eye diseases.

Adrenergic beta-Agonists↗

PubMed1995

The effect of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region in healthy young men.

The purpose of this study was to investigate the influence of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region and determine a potential autoregulative capacity of the choroid under these conditions. In a randomized cross-over study 100% O2 and a mixture of 5% CO2 with air was inhaled for 10 min by ten healthy male volunteers on different study days. Fundus pulsations were measured with a recently described laser interferometer. These results were compared to changes in systemic haemodynamics and Doppler-sonographic measurements of the radial artery. The fundus pulsation amplitude significantly decreased during hyperoxia and significantly increased during hypercapnia. These effects on fundus pulsations were stronger in the optic disc region than in the macular region. The systemic parameters showed only minor changes. Hence the amplitudes of fundus pulsations measured during hyperoxia and hypercapnia are assumed to be a consequence of metabolic autoregulative mechanisms. This autoregulative capacity is greater in the optic disc region than in the macular region, implying that the fundus pulsation amplitude in the papilla is influenced by both the choroidal and the retinal circulation.

Adult↗

PubMed1995

Is the ECG measure RSh a promising technique for detecting class I antiarrhythmic drug action in men?

Previous animal experiments suggest that the increase in the amplitude from the R-wave to the S-wave (RSh) may be more sensitive than other ECG measures to sodium channel blocking drug actions. We measured RSh of three orthogonal leads at baseline and during intravenous pharmacologic stimulation with adenosine, ajmaline, atropine, disopyramide, isoproterenol, lidocaine, norepinephrine (NE), propranolol, and verapamil in an observer-blinded placebo-controlled study in healthy young men. The short-term reproducibility of RSh was high. Ajmaline increased RSh in the anteroposterior lead, disopyramide in the anteroposterior and vertical lead, and lidocaine in the vertical and horizontal lead, respectively. Isoproterenol increased RSh in the anteroposterior lead; atropine decreased RSh in the vertical lead. The other drugs did not affect RSh significantly. Our data do not support the concept that RSh measure is a more sensitive technique for assessing class I antiarrhythmic drug action in humans, at least in healthy subjects. In addition, our results indicate that changes in autonomic tone may influence RSh measurements.

Adenosine↗

PubMed1995

Comparison of non-invasive methods for the assessment of haemodynamic drug effects in healthy male and female volunteers: sex differences in cardiovascular responsiveness.

1. The study was performed to determine the sensitivity and short-term and day-to-day variability of a novel technique based on laser interferometry of ocular fundus pulsations and of non-invasive methods for the quantification of haemodynamic drug effects. An additional aim was to assess sex differences in haemodynamic responsiveness to cardiovascular drugs in male and female healthy volunteers. 2. Ten males and nine females (age range 20-33 years) were studied in a double-blind, randomized, cross-over trial. Simultaneous measurements from systemic haemodynamics, laser interferometry of ocular fundus pulsations, systolic time intervals from mechanocardiography, a/b ratio from oxymetric fingerplethysmography and Doppler sonography of the radial artery were used to describe the haemodynamic effects of cumulative, stepwise increasing intravenous doses of phenylephrine, isoprenaline, sodium nitroprusside and of placebo. 3. Laser interferometry detected the isoprenaline-effects at the lowest dose level of 0.1 micrograms min-1 with a high signal-to-noise ratio. The reproducibility of measurements under baseline was high, no changes were observed after systemically effective doses of phenylephrine or sodium nitroprusside. Systolic time intervals were sensitive and specific for isoprenaline-induced effects, PEP and QS2c-measurements had high reproducibility. Fingerplethysmography proved a sensitive measurement for the detection of the vasodilating effects of sodium nitroprusside, but was not specific, and showed low reproducibility. Measurements from Doppler sonography had lower reproducibility and sensitivity compared with the other applied methods. 4. There was a significant sex difference for several of the haemodynamic parameters under baseline conditions; however, the responsiveness to the drugs under study was not different, when drug effects were expressed as %-change from the baseline. 5. Laser interferometry is a valuable non-invasive, highly sensitive and specific approach for the detection of pulse pressure changes. A battery of non-invasive tests appears useful for the characterization of cardiovascular drugs. Gender differences may not pose a relevant problem for the study of acute haemodynamic effects of cardiovascular drugs.

Adult↗

PubMed1995

Role of nitric oxide in hemostatic system activation in vivo in humans.

NO is a potent inhibitor of in vitro platelet aggregation and adhesion. In view of possible future widespread use of NO in pulmonary and cardiovascular diseases, we investigated the role of NO in hemostatic system activation in vivo in humans. Sixteen healthy male volunteers (age range, 22 to 33 years) received either NO by inhalation (50 ppm over 30 minutes; n = 8) or the NO synthase inhibitor NG-monomethyl L-arginine (L-NMMA 3mg/kg body weight i.v. over 5 minutes; n = 8), beta-Thromboglobulin (beta-TG), an indicator of platelet activity; prothrombin fragment 1 + 2 (F 1 + 2), an index of coagulation activation; and thromboxane B2 (TxB2), a measure of platelet prostaglandin synthesis, were determined in blood samples obtained from bleeding-time incisions ("shed blood") at baseline and after administration of the respective drug. In addition, beta-TG and F 1 + 2 were also determined in venous blood. To verify the systemic effects of the drugs, methemoglobin and plasma nitrites/nitrates were measured in the NO group, and cardiac output and exhaled NO were measured in the L-NMMA group. Compared with baseline, methemoglobin and plasma nitrates increased by 73 +/- 12% (P= .006) and 60 +/- 9% (P< .001), respectively, following NO inhalation. L-NMMA infusion resulted in decreases in both cardiac output by 16 +/- 2%; P< .001) and exhaled NO (by 54 +/- 7%; P< .001). NO inhalation or L-NMMA infusion had no significant effect on beta-TG, F 1 + 2, and TxB2 levels in shed blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1995

Short-term drug effects on the signal-averaged electrocardiogram in healthy men: assessment of intra- and interindividual variability of spectral temporal mapping and time-domain analysis.

The effect of cardiovascular drugs on the results of the signal-averaged electrocardiogram (SA-ECG) was studied in healthy young subjects. Cardiovascular drugs may confound the analysis of SA-ECG, but the effect of drugs on time-domain analysis and on spectral temporal mapping (STM) in healthy subjects has not been investigated under standardized conditions. Also, the reproducibility of the various spectral area measurements of STM has not been assessed simultaneously. Short-term drug effects on the SA-ECG were studied in 20 healthy young men (age 23.5 +/- 2.5 years) in an observer-blinded, crossover design on separate days. Each subject was randomly assigned to four drugs. The SA-ECG was recorded at baseline and during i.v. administration of stepwise increased doses of adenosine, atropine, isoproterenol, lidocaine, norepinephrine, propranolol, verapamil and placebo. Low amplitude signal duration was significantly and dose-dependently shortened by isoproterenol, whereas no consistent effect on the filtered QRS duration or on the root mean square voltage in the terminal 40 ms of time-domain analysis was noted for any of the other drugs. Only lidocaine significantly and dose-dependently decreased the parameters of STM at QRS offset and +20 ms, even though short-term reproducibility and day-to-day reproducibility of spectral area measurements were low. Interpretation of "normal" results from SA-ECG is not relevantly influenced by the studied drugs at clinical doses. STM may prove a useful technique for detection of the actions of sodium channel-blocking drugs. Reproducibility of STM measurements is substantially lower than that of time-domain parameters.

Adenosine↗

PubMed1990

Ventriculoarterial coupling influences regional contractility.

The purpose of this study was to adjudicate whether concomitant manipulation of inotropic state and arterial elastance influences linear indices of regional contractility. Fifteen autonomically denervated open-chest porcine hearts were instrumented with midmyocardial ultrasonic crystals and aortic and left ventricular chamber microamanometers. Linear left anterior descending coronary artery regional stroke work vs preload relationships (RSW) were generated by 10-sec vena caval occlusion at control and altered contractile states (either dopamine, 5 micrograms/kg/min, or propranolol, 0.2 mg/kg) and following arterial elastance variation (phenylephrine or nitroprusside), effecting an average 30% change in mean arterial pressure (MAP). Global contractility (dP/dt) was doubled (227% of control) by dopamine and halved (35% of control) by propranolol at constant preload (end-diastolic volume, end-diastolic pressure) and afterload (MAP). Regional contractility (RSW slope) was increased from 135 +/- 11 to 211 +/- 28, P less than 0.01, by dopamine, but unchanged with propranolol (106 +/- 10 vs 118 +/- 14, NS). Bidirectional changes in aortic elastance depressed the dopamine-augmented RSW slope (115 +/- 17, nitroprusside; 132 +/- 14, phenylephrine; P less than 0.01 vs dopamine). These differences were attenuated by propranolol infusion (98 +/- 7, nitroprusside; 132 +/- 9, phenylephrine; NS vs propranolol). Thus, optimizing ventriculoarterial coupling should supersede simple afterload manipulation in perioperative cardiac support.

Animals↗