[Preoperative internist consultation. II. Management in hypertension and cardiac disease].
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Cardiovascular Diseases↗
Biomedical subjects
T Thien
Publications and source records attributed to T Thien.
High-grade nucleoside transport inhibition stimulates ventilation in humans.
In 6 healthy male volunteers a placebo-controlled, double-blind, randomized, crossover trial was done to assess the effect of 1, 2, 4, and 6 mg of draflazine, a specific nucleoside transport inhibitor, on ventilation. Draflazine increased thoracic excursions dose-dependently by maximally (median with 95% confidence interval) 114.0% (38.3-184.8%) without affecting breathing rate. Ex vivo adenosine transport was inhibited by 0% (0-1%) after placebo, and 70% (59-74%), 81% (76-85%), 90% (86-93%), and 93% (90-96%) after the 4 increasing draflazine dosages, respectively (P < .05 for each draflazine dosage versus placebo). These results indicate that endogenously released adenosine may play a role in the regulation of ventilation.
Adenosine↗
Cardiovascular effects of sulphonylurea derivatives. Implications for the treatment of NIDDM?
Sulphonylurea derivatives are widely used in the treatment of non-insulin-dependent diabetes mellitus. The mechanism of action of the insulino-tropic effect of these agents is based on the closure of adenosine-5'-triphosphate (ATP)-sensitive potassium channels (KATP-channels) in the beta cells of the pancreas. In the last decade, these KATP-channels have been demonstrated in myocardial cells as well as in vascular smooth muscle cells. During myocardial ischaemia, the KATP-channels are thought to open by a fall in the cytosolic ATP concentration. The increase in the extracellular adenosine concentration, and the release of endothelium-derived hyperpolarizing factor (EDHF) during ischaemia may further contribute to the opening of cardiovascular KATP-channels. Independently from the mechanism of opening, sulphonylurea derivatives have been reported to block the opening of cardiovascular KATP-channels. Related to the role of KATP-channel-opening in the (patho)physiology of ischaemia, the use of sulphonylurea derivatives significantly modifies the outcome of experimental myocardial infarction. Sulphonylurea derivatives impair the recovery of the contractile function and increase the ultimate infarct size in animal models. In contrast, sulphonylurea derivatives have a beneficial effect on the incidence of ventricular fibrillation as occurs after ischaemic incidents of the myocardium. Based on these experimental observations, human studies are indicated to investigate whether the use of these drugs modifies the clinical outcome of cardiovascular events in patients with non-insulin dependent diabetes mellitus.
Animals↗
Urinary prostaglandin and prostaglandin metabolite excretion in patients with essential hypertension or hypertension with renal artery stenosis.
BACKGROUND: Recent studies have reported elevated prostaglandin levels in patients with renal artery stenosis and hypertension. To investigate whether a distinction between essential hypertension and hypertension with renal artery stenosis is possible by measuring eicosanoid excretion, we studied the excretion of these compounds in patients with essential hypertension and in hypertensives with concomitant renal artery stenosis. METHODS: The 24-h urinary excretion of metabolites of prostaglandin I2, prostaglandin E2 and metabolites of thromboxane A2 was sampled under standardised conditions, in 15 patients with essential hypertension and in 15 patients with unilateral renal artery stenosis with hypertension. Also clinical and biochemical characteristics of the subjects were analysed. RESULTS: The patients with renal artery stenosis had significantly lower excretion of prostaglandin I2 than did the essential hypertensive patients. However, the overlap in the values was large, thus not allowing a diagnostic differentiation according to urinary prostaglandin I2 levels. The excretion of prostaglandin E2 and of metabolites of thromboxane A2 showed no significant differences among the groups. CONCLUSIONS: Measurement of urinary prostaglandin or prostaglandin metabolite excretion did not contribute to the non-invasive detection of the presence of a renal artery stenosis in the patients in this study.
Adult↗
Hypertension and target organ damage.
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Cerebrovascular Circulation↗
Comparison of intrabrachial and finger blood pressure in healthy elderly volunteers.
This study was performed to compare continuous Finapres (FIN) and intrabrachial (IAP) blood pressure in healthy elderly volunteers. Fifteen elderly subjects (age 71 to 83) without cardiovascular disease and an intraarterial mean (range) systolic and diastolic blood pressure of 162 (122 to 195) and 73 (62 to 88) mm Hg, respectively, participated in the study. A 10-min head-up tilt, 10 min active standing, a 15-sec Valsalva, and a 5-min mental arithmetic were performed in random order. Beat-to-beat values of systolic, diastolic, and mean arterial pressure were analyzed. At rest, FIN underestimated IAP by 16.8 +/- 2.6 (SE), 10.8 +/- 1.5, and 17.5 +/- 1.6 mm Hg for systolic, diastolic, and mean arterial blood pressure, respectively (P < .05). During head-up tilt, FIN overestimated the intraarterial systolic blood pressure response by 7.2 +/- 1.6 (SE) mm Hg (P < .05). Group-averaged changes in diastolic and mean arterial IAP were followed closely by FIN. During standing, Finapres closely followed intraarterial diastolic and mean arterial pressure but the increase in systolic blood pressure was higher at the finger as compared to intrabrachial recordings, resembling the results of head-up tilt. During the Valsalva maneuver, maximal responses in systolic, diastolic, and mean arterial pressure were underestimated by FIN by 12.1 +/- 3.3 (SE), 6.8 +/- 2.7, and 7.1 +/- 1.7 mm Hg, respectively (P < .05 for all parameters). During mental arithmetic, FIN underestimated the intraarterial systolic blood pressure response by 6.1 +/- 2.7 (SE) mm Hg (P < .05), while diastolic and mean arterial pressure responses were followed correctly by FIN. It is concluded that apart from systolic blood pressure, FIN closely follows intraarterial blood pressure responses for the orthostatic maneuvers and mental arithmetic. During Valsalva, the rapid changes in blood pressure were followed in direction but not in magnitude.
Aged↗
Effect of long-term angiotensin-converting enzyme inhibition on endothelial function in patients with the insulin-resistance syndrome.
Cardiovascular risk factors such as hypertension, diabetes, and dyslipemia are associated with an impaired endothelium-dependent vasodilation. In patients with type 2 diabetes mellitus, these risk factors are frequently clustered. We investigated whether long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril can improve endothelium-dependent vasodilation in this particular group of patients. We selected 10 patients with type 2 diabetes and hypertension (age 59.4 +/- 3.2 years, body mass-index 29.7 +/- 1.5 kg.m-2, blood pressure 169 +/- 6/92 +/- 1 mm Hg, total cholesterol 6.6 +/- 0.3 mM). Using venous occlusion plethysmography, we recorded the increases in forearm blood flow (FBF) in response to three vasodilator stimuli: (a) 5 min of forearm ischemia, (b) infusion of the endothelium-dependent vasodilator methacholine (Mch) into the brachial artery (0.03, 0.3, and 1.0 micrograms/min/100 ml), and (c) intraarterial infusion of the endothelium-independent vasodilator sodium nitroprusside (SNP 0.06, 0.2, 0.6 microgram/min/100 ml). This procedure was repeated after 6 months of treatment with perindopril 4-8 mg/day. Forearm vascular resistance (FVR) was calculated by the quotient of the mean arterial pressure (MAP) and the FBF. Perindopril reduced blood pressure (BP) by 19/10 mm Hg (p < 0.05) and increased baseline FVR, but improved neither the maximal percentage decrease in vascular resistance induced by Mch (from -80 +/- 2 to -82 +/- 2%) nor that induced by SNP (from -73 +/- 3 to -72 +/- 3%). Perindopril decreased the FVR reached after the ischemic stimulus from 6.5 +/- 1.2 to 4.8 +/- 0.6 U (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin-Converting Enzyme Inhibitors↗
Double-blind, placebo-controlled study of intravenous prostacyclin on hemodynamics in severe Raynaud's phenomenon: the acute vasodilatory effect is not sustained.
In 12 patients with severe Raynaud's phenomenon (RP: ischemic ulcers or intractable pain despite use of narcotic analgetics), we studied the acute and long-term hemodynamic effects of epoprostenol on systemic and finger skin circulation. Epoprostenol was infused intravenously (i.v., initial infusion rate of 2 ng/kg/min, with a subsequent increase of 2 ng/kg/min every 30 min to the individually tolerated maximal dose of 8 ng/kg/min) in a triple, 5-h, double-blind, placebo-controlled cross-over study. During epoprostenol infusion, systolic blood pressure (SBP) remained stable, while diastolic BP (DBP) decreased (-8 mm Hg, p < 0.02), with a simultaneous increase in heart rate (HR + 14 beats/min, p < 0.001). Forearm blood flow (FBF) increased and forearm vascular resistance (FVR) decreased during epoprostenol as compared with placebo infusion (p < 0.01). Epoprostenol caused a significant increase in fingertip skin temperature (p < 0.01) as well as in laser Doppler flux (p < 0.02) before and after a standardized cooling test of the hand as compared with placebo. The increase in transcutaneous oxygen tension reached significant difference only during recovery (p < 0.02). No long-term improvement was noted during two additional cooling tests performed 1 and 6 weeks after the completed epoprostenol or placebo triple-infusion cycle. Repeated long-lasting epoprostenol infusion immediately improves the microcirculation, but these effects are not sustained after 1 week.
Adult↗
The influence of ulnar nerve blockade on skin microvascular blood flow.
Microvascular research is seriously hampered by the great temporal and spatial variability of the measured skin blood flow and variation in sympathetic vasomotor reflexes within and between persons. Therefore skin vasomotor reflexes were studied before and after ulnar nerve blockade within the same person, resulting in a temporal complete denervation of the fifth finger and partial denervation of the fourth finger. Skin temperature and laser Doppler flux (LDF) were registrated to measure predominantly arteriovenous shuntflow. Measurements were performed on the palmar tip of the second and fifth finger in nine healthy volunteers, at baseline, and during a sympathetic reflex test (i.e. inspiratory gasp) and postural response test. Beat-to-beat digital blood pressure was recorded from the third and fourth finger by a Finapres device. Baseline capillary blood cell velocity (CBV) was measured at the nailfold of the second and the fifth finger. After ulnar blockade baseline skin temperature, LDF and CBV increased significantly, with respectively (mean +/- SE) 3.2 +/- 0.9 degrees C, 20.9 +/- 5.9 relative perfusion units and 0.79 +/- 0.40 mm-1 s. The percentage LDF decrease of the fifth finger during inspiratory gasp was 48.2 +/- 5.3% before and 3.1 +/- 0.9% after blockade. The postural response test showed a decrease in LDF of the fifth finger with no significant difference before and after blockade, respectively 12.3 +/- 14.7% and 8.0 +/- 2.7%, while no difference was found in the increase in digital blood pressure in the denervated fourth finger compared to both the same finger before blockade and to the third non-blocked finger.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Flow Velocity↗
Neurohumoral antecedents of vasodepressor reactions.
Vasodepressor (vasovagal) syncope, the most common cause of acute loss of consciousness, can occur in otherwise vigorously healthy people during exposure to stimuli decreasing cardiac filling. Antecedent physiological or neuroendocrine conditions for this dramatic syndrome are poorly understood. This study compared neurocirculatory responses to non-hypotensive lower body negative pressure (LBNP) in subjects who subsequently developed vasodepressor reactions during hypotensive LBNP with responses in subjects who did not. In 26 healthy subjects, LBNP at -15 and -40 mmHg was applied to inhibit cardiopulmonary and arterial baroreceptors. All the subjects tolerated 30 min of LBNP at -15 mmHg, but during subsequent LBNP at -40 mmHg 11 subjects had vasodepressor reactions, with sudden hypotension, nausea, and dizziness. In these subjects, arterial plasma adrenaline responses to LBNP both at -15 and at -40 mmHg exceeded those in subjects who did not experience these reactions. In 16 of the 26 subjects, forearm noradrenaline spillover was measured; in the eight subjects with a vasodepressor reaction, mean forearm noradrenaline spillover failed to increase during LBNP at -15 mmHg (delta = -0.06 +/- (SEM) 0.04 pmol min-1 100mL-1), whereas in the eight subjects without a vasodepressor reaction, mean forearm noradrenaline spillover increased significantly (delta = 0.31 +/- 0.13 pmol min-1 100mL-1). Plasma levels of beta-endorphin during LBNP at -15 mmHg increased in some subjects who subsequently had a vasodepressor reaction during LBNP at -40mmHg. The findings suggest that a neuroendocrine pattern including adrenomedullary stimulation, skeletal sympathoinhibition, and release of endogenous opioids can precede vasodepressor syncope.
Hemodynamics↗
Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection.
In 12 healthy male volunteers (27-53 yr), a placebo-controlled randomized double blind cross-over trial was performed to study the effect of the intravenous injection of 0.25, 0.5, 1, 2, 4, and 6 mg draflazine (a selective nucleoside transport inhibitor) on hemodynamic and neurohumoral parameters and ex vivo nucleoside transport inhibition. We hypothesized that an intravenous draflazine dosage without effect on hemodynamic and neurohumoral parameters would still be able to augment the forearm vasodilator response to intraarterially infused adenosine. Heart rate (electrocardiography), systolic blood pressure (Dinamap 1846 SX; Critikon, Portanje Electronica BV, Utrecht, The Netherlands) plasma norepinephrine and epinephrine increased dose-dependently and could almost totally be abolished by caffeine pretreatment indicating the involvement of adenosine receptors. Draflazine did not affect forearm blood flow (venous occlusion plethysmography). Intravenous injection of 0.5 mg draflazine did not affect any of the measured hemodynamic parameters but still induced a significant ex vivo nucleoside-transport inhibition of 31.5 +/- 4.1% (P < 0.05 vs placebo). In a subgroup of 10 subjects the brachial artery was cannulated to infuse adenosine (0.15, 0.5, 1.5, 5, 15, and 50 micrograms/100 ml forearm per min) before and after intravenous injection of 0.5 mg draflazine. Forearm blood flow amounted 1.9 +/- 0.3 ml/100 ml forearm per min for placebo and 1.8 +/- 0.2, 2.0 +/- 0.3, 3.8 +/- 0.9, 6.3 +/- 1.2, 11.3 +/- 2.2, and 19.3 +/- 3.9 ml/100 ml forearm per min for the six incremental adenosine dosages, respectively. After the intravenous draflazine infusion, these values were 1.6 +/- 0.2 ml/100 ml forearm per min for placebo and 2.1 +/- 0.3, 3.3 +/- 0.6, 5.8 +/- 1.1, 6.9 +/- 1.4, 14.4 +/- 2.9, and 23.5 +/- 4.0 ml/100 ml forearm per min, respectively (Friedman ANOVA: P < 0.05 before vs after draflazine infusion). In conclusion, a 30-50% inhibition of adenosine transport significantly augments the forearm vasodilator response to adenosine without significant systemic effects. These results suggest that draflazine is a feasible tool to potentiate adenosine-mediated cardioprotection in man.
Adenosine↗
MRI in patients with suspected vascular parkinsonism.
To determine whether MRI can reveal more vascular lesions in patients clinically suspected of having vascular parkinsonism, we compared 15 such patients with 15 patients who had idiopathic Parkinson's disease and 10 hypertensive controls. Patients with suspected vascular parkinsonism had significantly more subcortical lesions than those with Parkinson's disease or hypertension. The cutoff point that best distinguished patients with suspected vascular parkinsonism from patients with Parkinson's disease was a 0.6% level of lesioned brain tissue volume. There were two types of vascular parkinsonism: one had an acute onset and lesions located in the subcortical gray nuclei (striatum, globus pallidus, thalamus); the other had an insidious onset and lesions diffusely distributed in the watershed areas.
Aged↗
Sudomotor function in human poikilothermia.
Hypohidrosis predisposes to hyperthermia and may indicate generalized thermoregulatory failure. To assess the sweating capacity in human poikilothermia, we performed a quantitative analysis of the central and peripheral sudomotor pathways in four women with acquired poikilothermia (aged 29 to 38 years) and nine controls. Heat challenge in a climatic chamber (ambient temperature 40 degrees C, 50% relative humidity) for 180 minutes revealed that both sweat secretion and evaporative weight loss were significantly lower in the patients than in the controls (p < 0.01). Temperature thresholds for thermal sweating were markedly elevated in at least two patients, whereas a third patient showed no sweating response. Stimulation of the eccrine sweat glands by intradermally injected acetylcholine during reduced core temperature (34.9 +/- 0.7 degrees C) revealed a significantly reduced sweating response in all patients (p < 0.01); the sudomotor response to pilocarpine iontophoresis was reduced or absent in three patients. We conclude that the generalized thermoregulatory sudomotor failure in these patients was attributable primarily to disorders of the central sudomotor drive; the impaired postganglionic sudomotor response is temperature related and possibly secondary to (long-standing) poikilothermia. Quantification of heat-dissipating capacity is pivotal for diagnosing severe thermolability and may help to prevent serious heat illness.
Acetylcholine↗
Clinical pharmacokinetics and efficacy of renin inhibitors.
The successful introduction of angiotensin converting enzyme (ACE) inhibitors in the treatment of patients with essential hypertension or heart failure has increased interest in the (patho)physiological role of the renin-angiotensin system (RAS). ACE is not only involved in the formation of angiotensin II from angiotensin I, but also inactivates vasoactive substances such as bradykinin and substance P. Accumulation of these substances during treatment with ACE inhibitors may contribute to both their therapeutic action and certain adverse effects associated with their use, such as cough and angioneurotic oedema. Renin inhibitors offer an alternative approach to inhibit the RAS. The major advantage of these, still experimental, drugs is their high specificity for the RAS since angiotensinogen is the only known substrate of renin. The currently available renin inhibitors are pseudopeptides that are rapidly taken up by the liver and excreted in the bile. Consequently, these drugs are subjected to a considerable first pass effect which limits their oral bioavailability. Additionally, plasma elimination half-life times are short and the duration of action is limited. Despite these shortcomings, single oral or intravenous administration results in a 80 to 90% inhibition of plasma renin activity and a slight reduction in blood pressure in patients with hypertension. The extent of blood pressure reduction is dependent on the patient's salt balance. After 1 week of oral treatment with the renin inhibitor remikiren, the antihypertensive effect was reduced in salt-repleted hypertensive patients. Subsequent intravenous administration of the drug did not further affect blood pressure, indicating that it was not the first pass effect that was limiting the efficacy of remikiren.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Highly sensitive and specific HPLC with fluorometric detection for determination of plasma epinephrine and norepinephrine applied to kinetic studies in humans.
An HPLC separation method combined with fluorometric detection was extended to enable simultaneous assessment of plasma 3H-labeled and endogenous epinephrine (E) and norepinephrine (NE). Forearm fractional extraction (FFE) of 3H-labeled E and NE and of endogenous E was measured in 40 healthy volunteers who were receiving a continuous infusion of 3H-labeled E and NE. Concentrations of arterial and venous E were 26.8 +/- 1.95 (mean +/- SE) and 6.8 +/- 0.75 ng/L, respectively. Arterial and venous NE and dopamine (DA) were also measured, with respective values of 140.7 +/- 8.5 and 192.1 +/- 15.1 for NE, and 13.1 +/- 0.78 and 11.3 +/- 0.70 ng/L for DA. The FFE of 3H-labeled E was slightly but significantly higher (0.790 +/- 0.016) than the that of either 3H-labeled NE or endogenous E (0.748 +/- 0.0146 and 0.745 +/- 0.0185, respectively; P < 0.001), the correlations being highly significant (r = 0.80, P < 0.001) in both cases. The small difference between the FFE of E and of 3H-labeled E allows the calculation of the apparent spillover of E. However, this spillover was negligible compared with forearm NE spillover (0.0112 +/- 0.0031 vs 1.369 +/- 0.128 ng/L per minute. The high sensitivity of this measurement of venous E widens the possibilities for studying E kinetics under physiological conditions.
Adult↗
Acute effects of flosequinan (BTS 49465) in untreated moderate to severe hypertension.
Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a recently direct-acting vasodilator that should cause relatively less reflex tachycardia, was given in a single oral dose of 200 mg to 10 untreated patients with moderate to severe hypertension. Flosequinan caused a fall in blood pressure (BP) from 181/116 +/- 7/4 to 161/102 +/- 5/4 mm Hg (P < 0.05). The proportional decrease of mean arterial pressure (MAP) was 14.6% (P < 0.01). Together with the decrease of BP an increase of heart rate from 79 +/- 5 to 96 +/- 5 beats/min occurred (31 +/- 4%, P < 0.01). Forearm blood flow increased insignificantly (NS) from 3.7 +/- 0.6 to 5.5 +/- 1.5 ml/100 ml/min together with a small decrease in forearm vascular resistance from 47 +/- 7 to 39 +/- 7 arbitrary units (NS). Forearm venous distensibility remained stable around 0.03% mm Hg (NS). Neurohormonal parameters showed the consequences of systemic vasodilation: noradrenaline rose from 1.25 +/- 0.10 to 2.88 +/- 0.34 nmol/l (P < 0.01), adrenaline from 0.16 +/- 0.03 to 0.35 +/- 0.10 nmol/l (NS), plasma renin activity from 2.33 +/- 0.46 to 3.27 +/- 0.73 ng/ml/h (P < 0.05) and aldosterone from 14.31 +/- 2.47 to 26.3 +/- 8.02 ng/ml (P < 0.05). The serum concentrations of flosequinan and its major metabolite were within the therapeutic limits. Nine patients experienced minor side-effects such as headache, nausea and palpitations. We conclude that flosequinan has hypotensive efficacy with signs of systemic counter-regulatory mechanisms but without a clear forearm vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Accuracy of an automatic blood pressure device: the Omron HEM403C.
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Blood Pressure Determination↗
Circulating adrenaline is not involved in the circadian blood pressure profile.
BACKGROUND: Circadian changes in blood pressure are paralleled by analogous circadian changes in plasma catecholamines: blood pressure, plasma noradrenaline and adrenaline fall at night. OBJECTIVE: To determine whether adrenaline is a prerequisite for the nocturnal fall in blood pressure, the circadian blood pressure profile was studied in adrenalectomized subjects, lacking circulating adrenaline. SUBJECTS AND METHODS: Ten adrenalectomized subjects and 10 healthy age-matched normotensive controls underwent 24-h non-invasive ambulatory blood pressure monitoring with the Oxford Medilog device. Measurements were taken every 15 min from 7.00 a.m. until 11.59 p.m and every 30 min from 12 midnight until 6.59 a.m. The nocturnal blood pressure fall was calculated for each subject. RESULTS: Mean +/- SD systolic blood pressure decreased at night by 13.2 +/- 9.5 mmHg in the adrenalectomized and by 11.7 +/- 7.3 mmHg (NS) in the control subjects. There was no significant difference between groups in the nocturnal diastolic blood pressure fall (14.4 +/- 5.1 and 13.1 +/- 5.2 mmHg, respectively). Systolic blood pressure decreased by > 10 mmHg in five of the adrenalectomized and eight of the control subjects. Diastolic blood pressure decreased by > 10 mmHg in eight of the adrenalectomized and eight of the control subjects. CONCLUSION: The normal nocturnal fall in blood pressure in adrenalectomized subjects indicates that circulating adrenaline is not required for a normal circadian blood pressure rhythm.
Adrenalectomy↗