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Biomedical subjects

Juha Koskenvuo

Publications and source records attributed to Juha Koskenvuo.

5 recordsLinked to original sources

Estimation of cardiac output in a pharmacological trial using a simple method based on arterial blood pressure signal waveform: a comparison with pulmonary thermodilution and echocardiographic methods.

OBJECTIVE: Cardiac output (CO) has traditionally been measured using invasive techniques, which involve an element of risk. Thus, a reliable less-invasive method for determining CO would be very valuable for research use. We tested whether simple analysis of the arterial pulse waveform, not requiring large-vessel catheterisation or expensive equipment, could provide an estimate of CO that is accurate enough for pharmacological studies. METHODS: We measured CO in 11 healthy male subjects who received low and high doses of dexmedetomidine (alpha2-adrenoceptor agonist), using pulse contour analysis, echocardiography and pulmonary thermodilution techniques. RESULTS: At baseline, these methods gave the following mean (SD) values of CO: 6.18 (1.59), 5.22 (1.35) and 7.03 (1.54) l/min, respectively. High-dose dexmedetomidine reduced CO to 4.50 (0.68), 3.65 (0.65) and 4.80 (0.89) l/min, corresponding to -25 (14) %, -28 (12) % and -30 (14) % reductions from baseline, respectively. The pulse contour method described these dexmedetomidine-induced changes in CO very similarly to the thermodilution and echocardiographic methods. The limits of agreement [bias (2SD)] were 0.55 (2.55) and -0.10 (2.04) l/min, respectively. CONCLUSION: The minimally invasive pulse contour analysis technique might be suitable for pharmacological studies for the detection of major drug-induced reductions in CO.

Adrenergic alpha-Agonists↗

Effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects.

BACKGROUND: Dexmedetomidine, a selective alpha2-adrenoceptor agonist, has counteracting effects on the cardiovascular system. It mediates sympatholysis by activating alpha2 adrenoceptors in the central and peripheral nervous system, and vasoconstriction and vasorelaxation by activating postsynaptic alpha2 adrenoceptors in blood vessels. The goal of this study was to determine the effects of therapeutic and high concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy subjects. METHODS: The authors studied 12 healthy young men. Myocardial blood flow (assessed with positron emission tomography), myocardial function (by echocardiography), and hemodynamic data were collected before and during low (measured mean plasma concentration, 0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine. RESULTS: The low concentration of dexmedetomidine reduced myocardial perfusion (mean difference, -27% from baseline [95% confidence interval, -31 to -23%], P < 0.001) in parallel with a reduction in myocardial oxygen demand (estimated by the rate-pressure product (-23% [-28 to -18%], P < 0.001). The high dexmedetomidine plasma concentration did not further attenuate myocardial perfusion (-3% [-12 to +6%] from low dexmedetomidine, P > 0.05; -29% [-39 to -18%] from baseline, P < 0.001) or statistically significantly affect the rate-pressure product (+5% [0 to +10%], P > 0.05). Systolic myocardial function was attenuated by sympatholysis during the low infusion rate and was further attenuated by a combination of the sustained sympatholysis and increased afterload during the high infusion rate. CONCLUSIONS: In healthy subjects, plasma concentrations of dexmedetomidine that significantly exceed the recommended therapeutic level do not seriously attenuate myocardial perfusion below the level that is observed with usual therapeutic concentrations and do not induce evident myocardial ischemia.

Adrenergic alpha-Agonists↗

Long-term alterations of heart rate dynamics after coronary artery bypass graft surgery.

We tested the hypothesis that there may be long-term alterations in overall heart rate (HR) variability and in fractal HR behavior after coronary artery bypass graft (CABG) surgery. Reduced HR variability predicts morbidity in various patient populations. Continuous 24-h electrocardiograph recordings were performed in 25 elective CABG surgery patients 1 wk before the operation and 6 wk and 6 mo after. Seventeen of the patients also had recordings 12 mo after CABG. Time and frequency domain measures of HR variability were assessed, along with measurement of short-term fractal scaling exponent (alpha1), approximate entropy, and power-law relationship of relative risk interval variability (beta-slope). The high, low, very low, and ultra low frequency powers decreased significantly after the operation and remained at a significantly decreased level 6 wk and 6 and 12 mo after the operation than before (P = 0.01, P < 0.001, P < 0.001, and P < 0.001 for overall difference between the time points, respectively). The fractal scaling exponent alpha1 was at significantly more decreased 6 wk after (P < 0.05) CABG than before surgery but recovered to the preoperative level 6 mo after the operation. Long-term fractal organization (beta-slope) remained stable, but the overall complexity (approximate entropy) decreased toward more predictable HR dynamics during the study period (P < 0.01 after 1 yr). The predictive value of temporary and persistent long-term changes of the HR dynamics after CABG surgery for long-term outcome is not clear.

Aged↗

Effects of common polymorphisms in the alpha1A-, alpha2B-, beta1- and beta2-adrenoreceptors on haemodynamic responses to adrenaline.

Common naturally occurring polymorphisms have been identified in the coding regions of the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoceptor (AR) genes [alpha(1A)-AR R492C, alpha(2B)-AR insertion/deletion (I/D), beta(1)-AR R389G, beta(2)-AR G16R and beta(2)-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160 ng/kg of body weight per min; 5 min for each infusion rate) before and after beta-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the alpha(1A)-AR R492C polymorphism was associated with a longer ECG PR interval before and during the adrenaline infusions. The deletion/deletion (D/D) genotype of the alpha(2B)-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before beta-blockade. The beta(1)-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the beta(2)-AR G16R polymorphism demonstrated increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was decreased in the other genotype groups. These results suggest that, upon acute adrenaline infusion, the alpha(2B)-AR D/D genotype confers increased vasoconstriction and that the beta(2)-AR GG genotype confers reduced vasodilatation.

Adrenergic beta-Antagonists↗