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Biomedical subjects

C de Mey

Publications and source records attributed to C de Mey.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Myrtol standardized in the treatment of acute and chronic respiratory infections in children. A multicenter post-marketing surveillance study].

This multicenter post-marketing surveillance study examined the course of characteristic signs and symptoms and the tolerability of myrtol standardized (Gelomyrtol/Gelomyrtol forte) in 511 children (4 to 12 years of age) with acute and chronic sinusitis, bronchitis and sinubronchitis. The choice of dose and formulation (120 mg or 300 mg myrtol stand) accounted for the patients' age and body weight. The following signs and symptoms were evaluated before and after 1 and 2 weeks of treatment: impaired nasal respiration (blocked-up nose), pain upon pressure on the trigeminal nerve endings, headache, sensitivity of the paranasal sinuses, presence of mucus in the pharynx. At the end of the observation period, the physicians, the patients themselves and their parents judged efficacy of the medication. In more than 90% of the children, trigeminal pain, headache, paranasal sensitivity, and mucus in the pharynx had disappeared after two weeks of treatment. In more than 60%, impaired nasal respiration and difficulty to evacuate sputum were no longer observed. The incidence of adverse drug reactions was low: less than 1%. The efficacy was judged to be very good or good by the majority of physicians, patients and parents. In spite of their young age, most children (> 80%) experienced no difficulty in swallowing the capsules.

Acute Disease↗
PubMed1997

Adverse events and discomfort in studies on healthy subjects: the volunteer's perspective. A survey conducted by the German Association for Applied Human Pharmacology.

OBJECTIVE: The various good clinical practice (GCP) guidelines do not define the volunteering subject as an active party. The present survey addresses the volunteer's perception of study-related inconvenience and risk and its impact on their decision to enroll. METHODS: The survey consisted of a questionnaire to be filled out voluntarily and anonymously by healthy subjects who volunteered for enrollment in human pharmacology studies and who had participated in at least one previous study. Twenty-five categorised multiple-choice questions covered previous study experience, motives for volunteering, perception of and compliance with study directives and restrictions, past experience with adverse events, impact of the study environment on perceived well-being and the nature of adverse events likely to discourage them from enrollment. RESULTS: Seven centres contributed by providing at least 30 (range 30-100) evaluable questionnaires. The database consists of a total of 440 healthy subjects (30.5% females, 69.5% males), from 18 to over 60 years of age. Two hundred and seven subjects (47.1%) were company employees and 233 (52.9%) were external volunteers. Eighty nine percent only participated in studies at one particular centre. Some 53.3% indicated financial motives, 27.8% 'contribution to an improvement of pharmacotherapy', 12.7% 'social responsibility', while 6.2% indicated other motives, mainly the opportunity of a free medical check-up. Thirteen subjects (3%) admitted to not answering correctly to the recruitment questions; this limited reliability is suspected to be even larger when the answer might preclude enrollment. From the volunteers' perspective, the environmental study conditions clearly appeared to have a highly relevant impact on their personal well-being. Some 17.1% of the subjects reported to have suffered adverse events occasionally and 2.7% frequently; but 14% admitted not reporting adverse events promptly and about 20% indicated that, with respect to previous adverse events, they first sought advice from other volunteers rather than from the investigator. CONCLUSIONS: Adverse events and inconveniences are inherent to nontherapeutic studies in healthy subjects. From the volunteer's perspective it appears that the incidence of adverse experiences in such studies exceeds the reported frequencies from investigators considerably. This finding suggests that investigators are usually not aware or able to ascertain the true incidence of adverse events. The present survey also confirms that pertinent information on the personal history may be unreliable. Volunteers are reluctant to answer questions regarding, in particular, their smoking habits, caffeine and alcohol consumption. Regarding the matter of informed consent, a noteworthy contradiction between the volunteers' attitude and behaviour became apparent. Although the volunteers admit that even rather minor adverse events ordinarily would discourage them, they still consent to enrollment. In view of this apparent contradiction, there is no alternative to the investigator's personal responsibility to counsel and protect the subject. Surveys such as this one may contribute to the awareness that the explicitness of GCP guidelines merely define the format, but not the content quality of these fundamental ethical values, which remain the unique burden and challenge of the investigator.

Adolescent↗
PubMed1997

Beta-adrenergic stimulation enhances left ventricular diastolic performance in normal subjects.

To determine the effects of beta-adrenergic stimulation on transmitral Doppler echocardiography flow characteristics of left ventricular diastolic filling, we studied 10 healthy volunteers aged 23-31 years (mean age, 26.6 years) during intravenous infusion of isoprenaline in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 min). Saline control infusion was given in the same manner in a crossover and blinded protocol. Compared with the infusion of placebo, stepwise increasing doses of isoprenaline caused a dose-related increase in early and late diastolic filling velocities and velocity-time integrals, a lengthening of the acceleration time, and a shortening of the deceleration and filling time. The chosen method proved highly sensitive, as statistically significant changes were detectable at the lowest dose of 0.1 microgram/min for all variables except velocity-time integral of late filling and deceleration time (> or = 0.2 microgram/min). The effects related to dose in a log-linear fashion except for the lengthening of the acceleration time (early ceiling), the increase of peak early filling velocity (increased steepness at higher doses), and the shortening of the filling time. Inclusion of the associated increases in heart rate and systolic blood pressure and the decrease in diastolic blood pressure blunted all treatment contrasts except for the increase of peak early filling velocity. In addition, the hemodynamics with respect to heart rate and loading conditions were not altered at low dosages of drug (< 0.4 microgram/min). Effects of at least the peak early filling velocity must be interpreted as an active adrenergically mediated myocardial relaxation process. These findings have potentially important clinical implications for this noninvasive, readily available, and convenient technique in clinical pharmacology, stress testing, and possibly therapeutic interventions in diastolic dysfunction in humans.

Adrenergic beta-Agonists↗
PubMed1997

Usefulness, usability, and quality criteria for noninvasive methods in cardiovascular clinical pharmacology.

Validation of study methods is a prerequisite for their usability. Empirical quality criteria based on test-theoretical principles are useful for this purpose. These criteria are discussed for several noninvasive methods used in cardiovascular clinical pharmacology: electrocardiography, systolic time intervals, blood pressure, and estimates of stroke volume. Several of these methods are highly reliable and sensitive to drug effects. However, they are inherently low in validity because they are based on oversimplified algorithms and yield estimates rather than measurements of function and changes therein. These estimates are method-specific and are likely to be subject to method*subject*effect interaction. Highlighting these constraints and the limitations of these methods need not preclude their useful contribution to the early evaluation of drug action in humans.

Animals↗
PubMed1997

Continuous measurement of hemodynamic alterations during pharmacologic cardiovascular stress using automated impedance cardiography.

The contribution of computerized impedance cardiography in monitoring and differentiating cardiovascular responses to pharmacologic stress after the administration of dipyridamole (group 1, n = 24) or dobutamine (group 2, n = 26) was investigated during stress echocardiography. Heart rate, stroke volume index, cardiac index and systemic vascular resistance index were evaluated continuously with an automated, computerized, signal-averaged impedance cardiography system. Dipyridamole had little average effect on heart rate, stroke volume index, and cardiac index. The responses were similar in patients with positive (n = 9) or negative (n = 15) stress echocardiography test results (as characterized by echocardiographic wall-motion abnormalities). Dobutamine induced a similar mean increase in heart rate in patients with negative (n = 13) or positive (n = 13) results on stress echocardiography. The mean increase in stroke volume index induced by dobutamine was greater in patients with negative stress echocardiography test results than in patients with stress-induced wall-motion abnormalities. This distinction was also seen in the cardiac index; the mean change in patients with negative stress echocardiography test results was larger than in patients with positive results. It is concluded that automated computerized impedance cardiography not only allows surveying and monitoring hemodynamic changes during pharmacologic stress echocardiography but also contributes to differentiation of pathologic stress responses.

Adult↗
PubMed1996

Differential effects of oral losartan and enalapril on local venous and systemic pressor responses to angiotensin I and II in healthy men.

This double-blind, placebo-controlled crossover study was designed to differentiate the pharmacodynamic effects of the angiotensin II receptor antagonist losartan from the angiotensin converting enzyme inhibitor enalapril. Effects of placebo, enalapril (10 mg), and losartan (20 and 100 mg) on local venous and systemic pressor responses to angiotensin I and II were compared in eight healthy male subjects. Treatments were administered orally approximately 4 hours before agonist infusions into a dorsal hand vein. Local changes in hand vein diameter and systemic blood pressure were monitored during the infusions. The 100 mg dose of losartan attenuated local venoconstrictor and systemic pressor responses to angiotensin I and II. In contrast, enalapril blocked only responses to angiotensin I. Both losartan and enalapril increased plasma renin concentration compared with placebo. These results are consistent with direct antagonism of angiotensin II receptors by losartan and with indirect effects of enalapril through inhibition of angiotensin converting enzyme.

Administration, Oral↗
PubMed1995

Clinical pharmacological equivalence of a novel FCH-free GTN spray with low ethanol content vs a FCH-containing GTN spray.

The overall therapeutic equivalence of a fluorochlorohydrocarbon (FCH)-free glyceryl trinitrate (GTN) pump spray with a low ethanol content (TL) was investigated relative to an FCH-containing GTN spray (Nitrolingual; R), in terms of: (1) pharmacokinetic bioavailability, (2) pharmacodynamic responses as assessed by digital plethysmography (DPG), and (3) clinical perception upon application. Pharmacokinetically, the time courses of the plasma concentrations of GTN and its dinitrate metabolites, 1,2- and 1,3-GDN, subsequent to the sublingual administration of 0.8 mg GTN showed somewhat lower bioavailability of GTN and its metabolites than to the reference. Pharmacodynamically, the changes in the DPG signals after the application of 0.8 mg GTN with TL were biostatistically equivalent with R (estimated ratio TL/R for the maximum decrease of the ratio between the systolic a wave and c incisure: 0.98; 90% CI: 0.84-1.14; and for the average decrease of the c: a ratio: 0.97; 90% CI: 0.80-1.16). The time of occurrence of the maximum effect of TL was not significantly different from that of R (estimated difference TL-R: -2.25 min; 95% CI:-9.5 min to 2 min). In contrast, after the administration of an FCH-free GTN spray with a higher ethanol content (TH, active control), the effect had a slightly earlier onset (TH-R: -6 min, 95% CI:-9.5 to -2 min) and there was a higher average response (TH/R: 1.12: 90% CI: 0.95 to 1.34). However, TH was consistently judged to cause an extremely unpleasant burning sensation in the mouth and thus was perceived as distinctly different from R. In contrast, TL was well tolerated and could not be distinguished from R.

Adult↗
PubMed1995

Dose-effect and kinetic-dynamic relationships of the beta-adrenoceptor blocking properties of various doses of talinolol in healthy humans.

Twelve healthy subjects were investigated on six separate occasions at least 1 week apart when they either received a single oral dose of 80 mg propranolol; 25, 50, 100, or 400 mg talinolol; or placebo (double-blinded, period-balanced six-way cross-over design). The subjects were investigated during supine rest and performed supine bicycle ergometry 0200, 0500, 0730, 1000, and 2400 h after dosing. Isoprenaline (ISO) and epinephrine (EPI) were infused intravenously (i.v.) at a constant infusion rate of 1 microgram/min for 10 min, at 0315 and 0400 h after dosing, respectively. At various timepoints, blood was drawn for the high-performance liquid chromatography (HPLC) determination of the plasma concentrations of talinolol's enantiomers and for the ex vivo in vitro determination of beta 1- and beta 2-adrenoceptor binding and related concentrations by radioreceptor assay (RRA). Talinolol was confirmed to bind to beta-adrenoceptors with moderate affinity but to act as a highly selective and efficient beta 1-adrenoceptor antagonist in terms of the relative degree and duration of its ergometric effects. At doses < or = 100 mg talinolol hardly altered the reduction of estimated vascular total peripheral resistance (TPR) in response to the intravenous infusion of ISO and EPI. Only at doses of 400 mg did talinolol more closely approximate the effects of propranolol, which lead to a loss of the vasodilatory actions of EPI ("EPI reversal"). On the average, there was a smoothly linear relationship between the ergometric treatment effects and log-transformed dose, the logtransformed concentrations of the S(-)-enantiomer measured by HPLC, and the RRA-derived estimated occupancies beta 1-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1994

Differential effects of the novel NO-donating drug pirsidomine and isosorbide dinitrate on the venous vascular bed.

Sixteen healthy male subjects were investigated on four occasions when they received either placebo, 10 mg isosorbide dinitrate (ISDN), or 2.5 or 10 mg pirsidomine, a novel NO-donating drug. A constant-rate iv. infusion of a subsystemic dose (average 42 ng.min-1, SD 20.5) of noradrenaline in a dorsal hand vein was begun 1 h before drug treatment. It did not cause systemic changes but reduced the venous hand vein diameter by about 50%. This venoconstrictor response was approximately halved by 10 mg ISDN. Pirsidomine, in contrast, did not affect the in situ venoconstrictor responses to noradrenaline. ISDN and pirsidomine reduced systemic resting blood pressure. ISDN and 10 mg pirsidomine were approximately equipotent in reducing systolic blood pressure, both in terms of the duration and the extent of the effect (maximum average reduction of ISDN -6.7, 95% CI -10.3 to -3.0; and 10 mg pirsidomine -7.6, 95% CI -11.3 to -4.0 mmHg, respectively); 2.5 mg pirsidomine was less effective (-4.1, 95% CI -7.8 to -0.5). ISDN and 10 mg pirsidomine were also similarly effective in reducing diastolic blood pressure (ISDN -8.4 mmHg, 95% CI -10.5 to -6.2; 10 mg pirsidomine -6.0 mmHg, 95% CI -8.2 to -3.9; 2.5 mg pirsidomine -2.8 mmHg, 95% CI -5.0 to -0.6) but the effects of ISDN were longer lasting. Although similar with regard to their putative mechanism(s) of action and likely arterial/arteriolar effects, pirsidomine and ISDN seem to affect the venous vascular bed in distinctly different ways.

Adult↗
PubMed1994

Dose-effect and pharmacokinetic-pharmacodynamic relationships of the beta 1-adrenergic receptor blocking properties of various doses of carvedilol in healthy humans.

OBJECTIVE: To evaluate the pharmacodynamic properties of carvedilol across a broad range of doses in relation to its enantiospecific kinetics and adrenergic receptor occupancies, relative to placebo and propranolol. METHODS: Twelve healthy male subjects were investigated on six separate occasions at least 1 week apart when they received either a single peroral dose of 40 mg propranolol, 12.5, 25, 50, or 100 mg carvedilol, or placebo. The subjects were extensively profiled at supine rest, and they underwent supine bicycle ergometry before and at 2, 4, 6, 9, 12, and 22 hours after dosing. At these time points blood was drawn for the high performance liquid chromatographic determination of the enantiomers of carvedilol and for the radioreceptor assay determination of alpha 1- and beta 1-adrenergic receptor binding and related concentrations. RESULTS: Carvedilol was confirmed to bind to beta 1-adrenergic receptors and (albeit to a lesser extent) to alpha 1-adrenergic receptors. Carvedilol furthermore attenuated the ergometric increase in heart rate in a closely dose-related fashion, which exemplified its beta 1-adrenergic receptor blocking effects. However, the basal efferent adrenergic drive might have been too low to show consistent alpha 1-blocking properties. The radioreceptor and enantiomer kinetics were proportional with dose. There was no indication that the overall kinetic behavior of contributing active metabolites would differ from that of the S(-)-enantiomer. On average, there was a smooth linear relationship between the ergometric treatment responses and log-transformed dose, log-transformed concentrations of the S(-)-enantiomer, and the radioreceptor assay derived beta 1-adrenergic receptor occupancies. CONCLUSION: The relative complexity of the kinetics of carvedilol (enantiospecific kinetics and dynamics, protein binding, and involvement of active metabolites) does not preclude relatively simple and straight-forward dose-effect and kinetic-dynamic relationships.

Administration, Oral↗
PubMed1994

Analysis of pharmacokinetic-dynamic interrelations with special reference to applications in cardiovascular clinical pharmacology.

The relationship between a (detectable) cardiovascular response and plasma concentrations is affected by 1. the temporal delay of the equilibrium between sampling site and effector site(s), 2. the intrinsic relationship between the primary effect(s) and concentration at the effector site(s) and 3. inter-pharmacodynamic processes that link the primary effects to a net response and that might attenuate or amplify the primary effects. Confounding factors (active metabolites, time-variant protein-binding, enantiospecific pharmacological behavior, physiological counter-regulation, etc.) might confuse the issue even more. Models that address kinetic-dynamic interrelations are usually confined to the first two processes listed above and hardly account for the third factor (and often are inadequate if more than one confounding factor is involved). They yield model-driven assimilative solutions that are characterized by a high level of indetermination. The "fit" of the experimental data with an analytical model (in itself usually quite appealing by its mathematical elegance and inductive creativity) should not be mistaken as a "match" between the model and physio-pharmacological "reality". In consequence, these models are cognitive constructions that provide important insight in the complexity of these physio-pharmacological processes without necessarily solving it. Their actual "proof" and ultimate value thus lies in their practical applicability (i.e. their effective instrumental use) to predict, correct and optimize (pharmacotherapeutic) response. Unfortunately most models have failed to be successfully tested in this regard.

Cardiovascular Agents↗
PubMed1994

[Pharmacodynamic equivalence and clinical trial of a new fluorocarbon-free glycerol trinitrate pump spray with low ethanol content in comparison to a fluorocarbon-containing reference spray and a fluorocarbon-free pump spray with high ethanol content].

The pharmacodynamic equivalence of a fluorohydrocarbons-(FCH)-free glyceryl trinitrate (GTN, CAS 55-63-0)-containing pump spray with low ethanol content (Nitrolingual-Spray N; TL) versus a conventional FCH-containing GTN spray (Nitrolingual-Spray, R) as reference and a FCH-free GTN pump spray with high ethanol content (TH) was investigated by digital plethysmography (DPG) in a double-blinded, placebo-controlled (TL-matched placebo spray), randomized, period-balanced, 4-way cross-over design. Additionally the clinical tolerability (as perceived by the subjects and reported to the treatments-administrating investigator) was determined. The DPG-changes (cla; ratio of c-incisure and systolic a-wave) after the sublingual (s.l.) administration of 0.8 mg GTN of TL were biostatistically equivalent with R: the confidence intervals (CI) of the point estimates of the maximal decrease in cla (TL/R: 0.98, 90%-CI: 0.84 to 1.14) and the area-weighted average decrease in cla (TL/R: 0.97, 90%-CI: 0.80-1.16) were well in a 80-125% tolerance range. The time of occurrence of the maximal DPG-effect of TL was not different from R (distribution-free estimate of the difference TL-R: -2.25 min, 95%-CI: -9.5 min to 2 min). In contrast the maximal DPG-effect of TH after the s.l. administration of 0.8 mg GTN had a statistically significant earlier onset (TH-R: -6 min, 95%-CI: -9.5 min to -2 min) and a higher area-weighted average response (TH/R: 1.12, 90%-CI: 0.95 to 1.34). TH consistently caused an utterly unpleasant burning sensation in the mouth, thus this perceived local discomfort was distinctly different compared to all other treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗
PubMed1993

Effect of pretreatment with the selective beta 1-adrenoceptor antagonist bisoprolol on the subsequent cardiovascular actions and beta-adrenoceptor subtype specific occupancy of celiprolol in healthy man.

The cardiovascular effects at rest and during exercise and beta 1- and beta 2-adrenoceptor occupancy following a single dose of 1200 mg celiprolol p.o. were investigated in 8 healthy subjects with or without pretreatment with a single dose of 20 mg bisoprolol p.o., using a placebo-controlled, 2-way cross-over design. The ergometric responses of heart rate (HR) and systolic blood pressure (SBP) after celiprolol were reduced to a similar extent as after bisoprolol, but the cardiovascular function at rest was affected in a different way: there was a rise in HR, clear enhancement of cardiac systolic performance, and a considerable drop in the estimated total peripheral vascular resistance, associated with median beta 1-RRA and beta 2-RRA occupancies of 88 and 34%, respectively. The cardiovascular effects of celiprolol were not affected by pretreatment with bisoprolol. Celiprolol thus binds extensively to beta 1-adrenoceptors, moderately to beta 2-adrenoceptors, acts as beta 1-adrenergic antagonist (exemplified by the ergometric effects) but has vasodilator, positive chronotropic and cardiac systolic performance enhancing properties, which do not involve either direct or indirect beta 1-adrenergic agonism, but which might reflect beta 2-adrenergic agonism.

Adult↗
PubMed1993

Pharmacokinetics of pantoprazole following single intravenous and oral administration to healthy male subjects.

The plasma pharmacokinetics of pantoprazole have been investigated following single intravenous infusion and single oral administration at a dose of 40 mg to 12 healthy male subjects in a randomised cross-over study. Both treatments were generally well tolerated and no relevant compound-related adverse events were noted. The plasma pharmacokinetics of pantoprazole following intravenous infusion in this group of subjects were characterised by a total plasma clearance of 0.13 l.h-1 x kg-1 and apparent terminal elimination half-life 1.9 h. The apparent volume of distribution estimated at steady state (0.17 l.kg-1) was compatible with the localization of a major fraction of the compound in extracellular water. Following oral administration as an enteric-coated tablet formulation, a variable onset of absorption was followed by rapid attainment of maximum plasma concentrations of pantoprazole. Pantoprazole was well absorbed following oral administration; the absolute systemic bioavailability of the compound was estimated as 77% (95% CI, 67 to 89%).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Captopril does not interact with the pharmacodynamics and pharmacokinetics of digitoxin in healthy man.

The chronic oral administration of 0.07 mg digitoxin o.d. for up to 58 days to 12 healthy volunteers caused a small drop in mean heart rate HR (95% CI: -7.9 to -1.6 beats.min-1), in mean diastolic blood pressure (95% CI: -8.3 to -0.4 mmHg), shortening of the QTc-interval (95% CI: -42 to -19 ms), shortening of the HR-corrected pre-ejection period PEPc (95% CI: -16 to -1 ms) and electromechanical systole QS2c (95% CI: -25 to -1 ms), and an increase in the impedance cardiographic Heather index (dZ/dtmax/RZ, 95% CI: 0.3 to 4.3) relative to the baseline measurements before digitalisation. The concomitant administration of 25 mg oral captopril b.d. did not significantly alter these responses relative to the concomitant double-blind administration of placebo, nor did it alter the pharmacokinetic characteristics of plasma digitoxin at steady state. Thus, no relevant change in the pharmacokinetic and pharmacodynamic characteristics of chronically administered digitoxin were induced by concomitant treatment with captopril.

Administration, Oral↗
PubMed1992

Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.

Adult↗
PubMed1992

Noninvasive estimates of the inodilatory effects of isoprenaline and their inhibition by transdermally delivered mepindolol in healthy men.

We analyzed the reproducibility and sensitivity of noninvasive estimates of cardiovascular performance (impedance cardiography and systolic time intervals) to detect and describe the inodilatory responses to isoprenaline (ISO) and their attenuation by transdermally applied mepindolol. The responses to 5-min intravenous (i.v.) infusions of 1 microgram/min ISO in 9 young male healthy volunteers were evaluated repeatedly before and at the end of chronic treatments with daily applied TSD skin patches for transdermal drug delivery with either mepindolol or placebo (double-blind randomized cross-over design). ISO caused a clear increase in mean heart rate (HR), systolic blood pressure (SBP), maximum velocity of impedance changes, estimated stroke volume (SV), and the Heather index, and a reduction in diastolic BP (DBP), estimated systemic vascular resistance (SVR), and a shortening of all systolic time intervals (STIs). These responses were effectively blunted at the end of 1-week treatment with mepindolol TSD patches. Despite overall good agreement of the mean baseline data (under placebo), their within-subject reproducibility nevertheless was too weak to guarantee adequate power to detect small changes under active treatment. Reproducibility of the ISO responses was quite poor, although in a method-independent way. The methods used allowed us to describe the cardiac and vascular components of the ISO responses with adequate detail. Transdermally delivered mepindolol was shown to block ISO responses effectively, but the overall variability of the responses was too large to detect slight changes in them, although the methods in themselves did not appear to be the main cause of this lack of sensitivity.

Administration, Cutaneous↗