Russell Ae

Transmitral velocities measured by pulsed Doppler in healthy volunteers: effects of acute changes in blood pressure and heart rate.

The effect of a two minute cold pressor test on transmitral velocities measured by pulsed Doppler was studied in 11 healthy volunteers. Blood pressure increased significantly during cold immersion but peak atrial and peak early diastolic transmitral velocities and their ratio (A:E) were unchanged. There was no correlation between changes in Doppler variables and changes in calculated mean arterial blood pressure during the test. Heart rate changes were variable and not related to changes in blood pressure. In individual people the change in pulse interval during cold immersion was significantly and inversely correlated with the change in the A:E ratio. The large acute increase in arterial pressure seen during the cold pressor test in normal volunteers had no consistent effect on the transmitral velocity profile although small changes in heart rate were associated with large changes in A:E ratio. The effect of small changes in heart rate may be of considerable importance in determining transmitral velocity profiles. Thus in clinical and experimental studies in which the heart rate is not controlled, Doppler data on transmitral flow should be interpreted with caution.

Automated non-invasive measurement of cardiac output: comparison of electrical bioimpedance and carbon dioxide rebreathing techniques.

Two commercial automated, non-invasive systems for estimation of cardiac output were evaluated. Values of cardiac output obtained by electrical bioimpedance cardiography (BoMed NCCOM3 machine) were compared with values derived from an indirect Fick technique that uses carbon dioxide rebreathing (Gould 9000 IV system) during 103 simultaneous measurements made at rest in 19 randomly selected subjects and on exercise in 11 subjects. Cardiac output values obtained with impedance cardiography were significantly correlated with those measured by the indirect Fick method, although there was a wide scatter with over 73% of the readings lying outside the limits defined by the line of identity +/- 20%. This correlation was greatly reduced when stroke volume index was used instead of cardiac output. Indirect Fick results were linearly related to oxygen uptake both at rest and on exercise, while impedance cardiography results did not correlate with oxygen uptake. Impedance cardiography gave consistently lower results for cardiac output than indirect Fick at all levels of exercise. Both machines were easy to use and produced acceptable mean (SE) coefficients of variation (BoMed NCCOM3 7.7 (1.0)%, Gould 9000 IV 10.6 (1.4)%). Further validation is required before either of these machines can be recommended as an alternative to invasive monitoring in clinical practice.

Enalapril and Atenolol in Essential Hypertension: Attenuation of Hypotensive Effects in Combination

In 16 patients with essential hypertension the effects of enalapril 20 mg once daily were compared with those of atenolol 50 mg once daily, with the two drugs in combination and with placebo using a double-blind cross-over design with allocation of treatment order by randomised Latin squares. For each patient there were four treatment phases, each of four weeks duration, which together comprised a 2 x 2 factorial experiment. All blood pressure parameters were reduced in the three active treatment phases compared to placebo (p less than 0.001). Supine blood pressures (group means) were 171/97 (placebo), 147/85 (enalapril), 154/84 (atenolol) and 144/78 (enalapril plus atenolol) (S.E.M. +/- 2/+/- 1-ANOVA), and standing blood pressures were 170/105 (placebo), 146/92 (enalapril), 154/92 (atenolol) and 147/86 (enalapril plus atenolol) (S.E.M. +/- 3/+/- 1). In the combination phase there was an additional hypotensive response but the potential fully additive effects of the two agents were attenuated by 30-50%. The mechanism of the attenuated hypotensive effect of the combined agents has not been determined. Plasma atrial natriuretic peptide (ANP) concentration was doubled in the presence of atenolol (P less than 0.01) suggesting that ANP may contribute to the hypotensive effect of the beta-blocker.

Automated non-invasive measurement of cardiac output by the carbon dioxide rebreathing method: comparisons with dye dilution and thermodilution.

The accuracy and reproducibility of indirect measurement of cardiac output at rest by the carbon dioxide rebreathing (indirect Fick) method with an automated respiratory analysis system (Gould 9000IV) were compared with simultaneous measurements made in duplicate by dye dilution and thermodilution in 25 patients having cardiac catheterisation studies. Measurements of cardiac output by the carbon dioxide rebreathing method were not significantly different from those obtained with dye dilution (mean difference -0.3 l/min, SD 0.76, 95% confidence interval -0.7 to 0.1). Thermodilution significantly over-estimated cardiac output by a mean of 2.2 l/min or 39% (SD 1.5, 95% confidence interval 1.6 to 2.8) compared with the carbon dioxide rebreathing method and significantly overestimated cardiac output by 1.9 l/min or 31% (SD 1.2, 95% confidence interval 1.2 to 2.5) compared with dye dilution. The reproducibility of measurements of cardiac output in individual patients was satisfactory with the dye dilution method but was poor with carbon dioxide rebreathing and thermodilution. Indirect measurement of resting cardiac output by the Gould 9000IV automated carbon dioxide rebreathing method is more accurate but the variability inherent with this method requires that multiple measurements be taken for each determination. Measurement of cardiac output by the thermodilution method by a commercially available cardiac output computer was not satisfactory because not only was there considerable variability between repeat measurements but the method also consistently overestimated cardiac output compared with the dye dilution method.

CIRCULATING SURFACTANT PROTEIN-B LEVELS INCREASE ACUTELY IN RESPONSE TO EXERCISE-INDUCED LEFT VENTRICULAR DYSFUNCTION

1. As a result of its enormous surface area and necessary thinness for gas exchange, the alveolocapillary barrier is vulnerable to mechanical disruption from raised pulmonary microvascular pressure (Pmv).

Diltiazem and atenolol in essential hypertension : additivity of effects on blood pressure and cardiac conduction with combination therapy

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance = 3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184s) compared with either diltiazem (0.175s) or atenolol (0.174s) alone, or placebo (0.164s); s.e.m. by analysis of variance = 0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.

Effect of Indomethacin on Blood Pressure Control during Treatment with Nitrendipine

This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist. Fifteen essential hypertensives (ages 58-80 years) had a supine diastolic blood pressure (DBP) < 100 mmHg after 4 weeks monotherapy with nitrendipine 5-20 mg twice daily. They entered a double-blind randomised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration. Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared. Supine blood pressure (mean +/- SE) was higher in the indomethacin phase (158 +/- 4/80 +/- 2) than in the placebo phase (154 +/- 4/76 +/- 3) (p < 0.01 for DBP). In 6/15 (40%) of subjects the increase in supine diastolic blood pressure with indomethacin was > 5 mmHg. Plasma urea was also increased in the indomethacin phase: 7.6 +/- 0.6 mmol/l compared with placebo: 6.3 +/- 0.5 mmol/l (p < 0.001). The study has demonstrated that concurrent treatment with the NSAID indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine. This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine. This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects.

Felodipine Monotherapy in Systolic Hypertension in the Elderly

Summary12 untreated subjects (ages 59–84 years; 9 male, 3 female) with isolated systolic hypertension participated in a single-blind dose-ranging study to assess the hypotensive effect and tolerability of felodipine. With dosing periods of 2 weeks’ duration, after a placebo run-in phase, felodipine was commenced at 2.5mg twice daily and increased to 5mg and then 10mg twice daily if predose systolic blood pressure was > 160mm Hg and diastolic blood pressure was > 70mm Hg. Nine subjects completed the study. At the highest attained felodipine dose, blood pressure 2 hours after the first dose was reduced by 25/12mm Hg supine and 26/17mm Hg standing compared with the placebo run-in phase. 12 hours after the last dose blood pressures were also lower than those in the placebo run-in phase but were similar to values after the placebo washout phase. The sequential design of this study has thus not allowed separation of treatment and period effects. Withdrawals were for vasodilator adverse effects, intercurrent illness and blood pressure below criteria for continuation. Four of the 9 patients completing the study also reported vasodilator side effects. It was concluded that a felodipine dose range of 2.5 to 10mg twice daily is appropriate for further studies in this patient group.