Differentiation of inodilatory responses by non-invasive measures of cardiovascular performance in healthy man.
The cardiovascular responses to various inodilatory interventions were investigated noninvasively in healthy man by monitoring heart rate (HR), blood pressure (SBP/DBP, according to Korotkoff I and IV criteria), systolic time intervals (PEP, VET and QS2) and impedance cardiographic estimates of stroke volume (SV) and cardiac output (CO). The following inodilatory interventions were evaluated and compared: the i.v. infusion of adrenaline (1 microgram/min), the i.v. infusion of isoprenaline (1 microgram/min) with and without pretreatment with 100 mg talinolol (a beta 1-selective beta-adrenoceptor antagonist), the p.o. administration of 1200 mg celiprolol (a beta 1-adrenoceptor antagonist with ancillary beta-adrenergic agonistic properties at the chosen dose level), the p.o. administration of 0.4 mg bimakalim (a K+ channel activator without direct cardiac effect) with and without pretreatment with 5 mg bisoprolol and the p.o. administration of the PDE-III inhibitors meribendan and isomazole. The extent of the inodilatory rise of HR, shortening of PEP, rise of SV and CO relative to the associated reduction of the calculated total peripheral resistance (TPR) proved a powerful tool to differentiate inodilatory properties: adrenaline, isoprenaline after beta 1-selective beta-adrenoceptor blockade and celiprolol led to similar ancillary adrenaline-like cardiovascular changes relative to the vasodilatation; bimakalim led to similar associated changes except for a relatively larger rise in HR, which could be blocked by bisoprolol; isoprenaline induced clearly larger associated changes, for which HR, VET, and QS2c were particularly sensitive; meribendan and isomazole resulted in the largest ancillary changes, characterized by a critical shortening of the ejection time VET, so that the rise of CO was almost exclusively defined by the rise of HR. These differences could be detected and differentiated sufficiently and adequately by HR, SV, CO, TPR, PEP, and VET. There seems little value in using more assumptive variables such as HR-corrected VETc and QS2c, the Weissler index and the impedance cardiographic Heather index.
De Mey
C
C
IPHAR Institute for Clinical Pharmacology, Höhenkirchen, Germany.
Erb
K
K
Schroeter
V
V
Belz
G G
GG
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000328:Adult; D001578:Benzopyrans / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D017272:Celiprolol / Q000494:pharmacology*; D018592:Cross-Over Studies; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008991:Monitoring, Physiologic
D001578:Benzopyrans; D002316:Cardiotonic Agents; D004095:Dihydropyridines; C061050:bimakalim; D017272:Celiprolol; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D007545:Isoproterenol