Use of the systolic time intervals in clinical pharmacology.

1 We have examined the problem of how systolic time intervals (STI) should be corrected for heart rate in clinical pharmacological studies. 2 'Individual' linear regression equations describing the relationship between STI and heart rate were derived for each of 43 healthy young adults (30 men and 13 women) by measuring STI at different heart rates produced by incremental doses of intravenous atropine. 'Population' equations for each sex were obtained by taking the mean of the 'individual' regression coefficients. 3 In order to assess which method more effectively reduced variability of the STI, 'individual' regression coefficients were derived for eight men who had previously participated in a placebo-controlled study which had used STI to test the cardiovascular effects of calcium antagonists alone and in combination with propranolol. 4 Within-subject variability in rate-corrected STI was similar after application of 'individual' and 'population' regression equations. Between-subject variability tended to be less after the use of 'population' equations. 5 'Population' regression equations were more effective than 'individual' regression equations in allowing detection of differences between treatments, as judged by F values from ANOVA.6 In clinical pharmacological studies including measurements of STI in healthy young subjects, 'individual' regression equations appear to have no advantage over 'population' equations derived in a group of subjects of similar age and sex.

Section: Methods Is Non-mentioning

confidence: 99%

Correction of systolic time intervals for heart rate: a comparison of individual with population derived regression equations.

Warrington

Weerasuriya

Burgess

1988

“…This effect of /3-adrenoceptor blockade on T-wave height has been reported previously (Stem & Eisenberg, 1969). Epoprostenol caused a reduction in PEP: this result is expected if peripheral resistance or arterial pressure falls and/or a positive inotropic action is exerted (Gibson, 1978).…”

Section: Discussionmentioning

confidence: 99%

The cardiovascular and platelet effects of epoprostenol (prostacyclin, PGI2) are unaffected by beta‐adrenoceptor blockade in man.

Hassan¹,

Pickles²,

Fish³

et al. 1982

1 Atenolol 0.2 mg/kg i.v., propranolol 0.2 mg/kg i.v. or placebo were given in a double‐blind crossover study to six healthy male subjects, and the effects of a subsequent infusion of epoprostenol (prostacyclin, PGI2) 0‐6 ng kg‐1 min‐1 monitored. 2 PGI2 caused a tachycardia, a fall in diastolic blood pressure, a rise in pulse pressure, reduction in pre‐ ejection period (PEP) and rise in left ventricular ejection time index (LVETI), headache and facial flushing at doses of PGI2 greater than 2 ng kg‐1 min‐1, (P less than 0.05). 3 Beta‐adrenoceptor blockade did not prevent the tachycardia in response to PGI2, and did not interact with any of the other dynamic effects of PGI2. 4 In vitro, PGI2 at 1 and 2 ng/ml inhibited platelet aggregation to ADP (P less than 0.01), although no significant effect on platelet aggregation was seen in the in vivo study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect this in vitro study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect in vitro effect of PGI2 on platelet aggregation. 5 Pretreatment with atropine 0.04 mg/kg i.v. in three subjects did not attenuate the tachycardia caused by PGI2 infusion, even though the baseline heart rate was increased. 6 Adverse effects to PGI2 infusion included sudden bradycardia, pallor and sweating, suggesting that the Bezold‐Jarisch reflex seen in animals in response to PGI2 may also occur in humans. 7 Neither increased sympathetic drive nor vagal withdrawal are likely causes of the tachycardia following PGI2 infusion.

“…These noninvasive techniques-as they relate to drug studieshave been usefully reviewed by Gibson (1978Gibson ( , 1979.…”

Section: Discussionmentioning

confidence: 99%

Haemodynamic effects of BM 10.188, a new orally active inotropic agent, in healthy volunteers.

Whiting¹,

Kelman²,

Sumner³

et al. 1982