Cardiac positron emission tomography imaging with [11C]hydroxyephedrine, a specific tracer for sympathetic nerve endings, and its functional correlates in congestive heart failure.

The integrative mechanisms of autonomic dysfunction in congestive heart failure (CHF) remain poorly understood. We sought to study cardiac retention of [11C]hydroxyephedrine (HED), a specific tracer for sympathetic presynaptic innervation, and its functional correlates in CHF. Thirty patients with mild to moderate heart failure underwent resting cardiac HED positron emission tomography imaging, spectrum analysis testing of systolic pressure and heart rate variability in the resting supine and 70 degrees head-up tilt positions, and testing of baroreflex sensitivity. Compared with control subjects, global myocardial HED retention index was reduced by 30% (p <0.01) in patients with CHF. The HED retention index did not correlate significantly with heart rate variability. However, it correlated with baroreflex sensitivity at rest (r = 0.43, p = 0.05) and with systolic pressure low-frequency (0.03 to 0.15 Hz) variability at head-up tilt (r = 0.76, p <0.01), as well as with low-frequency systolic pressure variability response from baseline to tilt (r = 0.75, p <0.01). We conclude that cardiac HED retention is reduced in patients with CHF. This correlates with blunted vascular sympathetic effector responses during posture-induced reflex activation and baroreflex control of heart rate, suggesting an interdependence between cardiac presynaptic innervation abnormalities and neural mechanisms important to blood pressure maintenance in CHF.

Effects of tocolytic treatment with ritodrine on cardiovascular autonomic regulation.

OBJECTIVE: To study the acute effects of tocolytic treatment with intravenous ritodrine on cardiovascular autonomic regulation. DESIGN: Validated methods to assess cardiovascular autonomic nervous function-heart rate and blood pressure variability and vagal cardiac baroreflex sensitivity-were measured before and during ritodrine infusion. SETTING: Turku University Central Hospital, Turku, Finland. SAMPLE: Twelve pregnant women admitted to hospital for threatened preterm labour. METHODS: Electrocardiogram and continuous noninvasive finger blood pressure signals were recorded in each woman, resting in a supine position. Autoregressive spectrum analysis was used to quantify short term heart rate and blood pressure variability. Vagal cardiac baroreflex sensitivity was measured as the bradycardia response to an intravenous bolus injection of phenylephrine. MAIN OUTCOME MEASURES: Vagal cardiac baroreflex sensitivity and spectrum analysis indices of short term heart rate and blood pressure variability. RESULTS: Ritodrine significantly decreased vagal cardiac baroreflex sensitivity as well as total (0.00-0.40 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power bands of the heart rate variability spectrum. Ritodrine significantly increased mean heart rate and the low frequency power band of the systolic blood pressure variability spectrum. CONCLUSIONS: In pregnant women with threatened preterm labour intravenous administration of ritodrine decreases vagal cardiac baroreflex sensitivity and vagal modulation of heart rate, and increases sympathetically mediated blood pressure variability. Decreased baroreflex sensitivity and heart rate variability are known to be associated with a poor prognosis in some patient groups, so the effects of ritodrine tocolysis may be unfavourable in women with impaired circulatory homeostasis.

Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril.

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

Low-dose transdermal scopolamine decreases blood pressure in mild essential hypertension.

BACKGROUND: Increasing cardiovascular parasympathetic nervous activity could have antihypertensive effects. Low-dose transdermal scopolamine increases vagal-cardiac modulation of sinus node and baroreflex sensitivity in healthy subjects and in cardiac patients. OBJECTIVE: To study the short-term effects of transdermal scopolamine on blood pressure and cardiovascular autonomic control in patients with mild essential hypertension. DESIGN: A randomized, double-blind, placebo-controlled crossover trial with 12 untreated middle-aged [aged 39+/-5 years (mean+/-SD)] patients with mild essential hypertension. METHODS: We recorded the electrocardiogram, auscultatory sphygmomanometric and continuous photoplethysmographic finger arterial pressure, and spirometry signals with patients supine and 70 degrees tilted during controlled (0.25 Hz) breathing. Cardiovascular autonomic regulation was analyzed with power spectrum analysis of R-R interval and arterial pressure variability and a spontaneous sequence method for baroreflex sensitivity. In addition, a deep-breathing test was performed to assess maximal breathing-related sinus arrhythmia. RESULTS: Transdermal scopolamine treatment significantly decreased blood pressure both when patients lay supine and when they were in the 70 degrees tilted position. Scopolamine also slowed heart rate and increased baroreflex sensitivity and R-R interval high-frequency variability for both body positionings. In addition, scopolamine accentuated respiratory sinus arrhythmia during deep breathing and blunted the tilt-induced increase in heart rate. Scopolamine did not affect blood pressure variability. CONCLUSIONS: Transdermal scopolamine decreases arterial pressure, increases baroreflex sensitivity and accentuates vagal-cardiac modulation of sinus node in patients with mild hypertension. Our study supports the hypothesis that increasing cardiovascular parasympathetic activity could have antihypertensive effects in essential hypertension.

Valsalva manoeuvre can be used to study baroreflex sensitivity in pregnancy.

OBJECTIVE: The aim of this study was to assess whether baroreflex sensitivity can be measured in a non-invasive manner with the Valsalva manoeuvre in pregnancy. STUDY DESIGN: Baroreflex sensitivity was measured from the reflex response to phenylephrine injection and phase four of the Valsalva manoeuvre in nine pregnant women at 27 (range 24-33) gestational weeks. RESULTS: Both the phenylephrine test and the Valsalva manoeuvre yielded similar estimates of baroreflex sensitivity (9.3 (4.1) ms/mmHg vs. 8.0 (5.2) ms/mmHg, Pearson's correlation coefficient r = 0.81, P < 0.008, linear regression BRSValsalva (ms/mmHg) = 1.03 x BRSPhenylephrine + 1.59). Comparable changes in heart rate and blood pressure were obtained with the phenylephrine test and the Valsalva manoeuvre. CONCLUSION: The physiological challenge caused by the Valsalva manoeuvre can be used to measure baroreflex sensitivity in pregnancy. A possibility to study baroreflex function non-invasively, without pharmacological intervention, benefits future research of blood pressure regulation in pregnancy.

Response of serum total renin to ramipril and metoprolol in hypertensive patients.

Renin-angiotensin system has long been thought to be a classic endocrine negative feedback system in the pathophysiology of hypertension. Furthermore, angiotensin II formation was believed to be regulated by renin secreted from the kidneys. In contrast to these considerations is the identification of local angiotensin II production in other tissues than pulmonary vasculature. Prorenin, the molecular precursor of renin, has been assumed to be involved in local angiotensin II production because of its renin-like activity. Prorenin has also been found to be secreted from extrarenal sources, although a major part of it is derived from the kidneys. Increased concentration of total renin in serum has been proposed to be useful in identifying patients with active proliferative retinopathy in insulin-dependent diabetic patients. Renin-angiotensin system is strongly affected by angiotensin-converting enzyme (ACE) inhibitors and therefore the interfering effect of ACE inhibitor medication on total renin concentration should be known in order to interpret serum total renin concentrations. Nine hypertensive outpatients, all men, treated at the department of internal medicine in Turku University Central Hospital, received randomly 5 mg of ramipril or 95 mg of metoprolol once a day for 4 weeks. Ramipril significantly increased the mean value of total renin (191.9 ng/l vs 312.0 ng/l, p < 0.01), but the metoprolol-induced increase in the concentration of serum total renin was insignificant. We conclude that the negative feedback mechanism in regulating renin and prorenin secretion was inhibited by ACE inhibitor ramipril but beta 1-selective adrenoceptor antagonist metoprolol did not significantly change total renin concentration in serum.

Effects of ramipril on the hormone concentrations in serum of hypertensive patients.

The effects of the angiotensin-converting enzyme inhibitor ramipril on thirteen endocrinological tests were evaluated. These tests comprised serum follitropin, lutropin, prolactin, thyrotropin, free thyroxine, total thyroxine, free triiodothyronine, parathyrin, cortisol, testosterone, sex hormone binding globulin, androstenedione and dehydroepiandrosterone sulphate. Eleven hypertensive outpatients, 9 men and 2 women, treated at the department of internal medicine in Turku University Central Hospital, received 5 mg of ramipril once a day for the study period of four weeks. The above mentioned endocrinological tests were performed before and at the end of the ramipril treatment. Ramipril decreased the value of free thyroxine statistically significantly, p = 0.011, from the mean value of 17.1 pmol/l to the mean value of 16.0 pmol/l when measured with Amerlex-MAB* free thyroxine kit. The mean within-subject difference was -1.10 pmol/l with a 95% confidence interval of -1.87 - -0.33 pmol/l. With the AutoDELFIA free thyroxine kit and with the reference method dialysis+RIA no effect was detected. Other endocrinological tests examined were not affected by ramipril. Since the decreasing effect of ramipril on free thyroxine was detected only with Amerlex-MAB* but neither with AutoDELFIA nor with dialysis+RIA, the effect was concluded to be analytical. The underlying mechanism and the component ultimately interfering with the analysis is unknown.

Effects of low-dose transdermal scopolamine on autonomic cardiovascular control in healthy young subjects.

We studied how posture influences the effects of transdermal scopolamine on autonomic cardiovascular regulation in a randomized, double-blind, placebo-controlled crossover study of 10 healthy young volunteers. We recorded the electrocardiogram and auscultatory sphygmomanometric and continuous non-invasive finger arterial pressure (Finapres device) to obtain signals for the beat-by-beat R-R interval and systolic, mean and diastolic pressures. R-R interval and arterial pressure variabilities were characterized by power spectral analysis. Scopolamine increased the mean R-R intervals and reduced arterial pressure in both the supine and the standing positions, but did not affect blood pressure variability. Scopolamine increased the total variability of R-R interval and its mid- (0.07-0.15 Hz) and high- (0.15-0.40 Hz) frequency band power in the standing position during controlled breathing at 0.25 Hz. In the supine position, scopolamine did not affect R-R interval variability. In the deep breathing test, scopolamine increased the maximal expiratory-inspiratory R-R interval ratio. This study showed that low-dose scopolamine increases vagal cardiac inhibition in both supine and standing positions in healthy volunteers. However, scopolamine increases heart rate variability only in the standing position during partial vagal withdrawal. The study also demonstrates that transdermal scopolamine decreases blood pressure in healthy young subjects.