Minutes Of Tilt Research Articles

Mesenteric blood flow during vasovagal syncope

s selected for presentation 3.6 Mesenteric blood flow during vasovagal syncope D. Jardine, R. Pointon, I. Wright, T. Buckenham Department of General Medicine, Christchurch Hospital, New Zealand Department of Nuclear Physics, Christchurch Hospital, New Zealand Department of Radiology, Christchurch Hospital, New Zealand Rapid vasoconstriction of the splanchnic arterioles, controlled by the sympathetic nervous system is thought to be the most important mechanism for maintaining blood pressure during posture change, exercise and haemorrhage. It has been hypothesised that during vasovagal reactions, the baroreflexes transiently fail, allowing blood to pool in the splanchnic vessels. This results in decreased venous return and a steady fall in stroke volume output during the minutes preceding syncope.We aimed tomeasure mesenteric artery blood flow during tiltinduced syncope to see if “active” vasoconstriction was maintained as blood pressure fell.We selected 40 patients with a history of fainting and during 70-degree head-up tilt, we continuously monitored blood pressure [MAP] [Finapress], heart rate [HR] and muscle sympathetic nerve activity [MSNA]. We also did pulsed-doppler measurements from the superior mesenteric artery each minute. Using the pixel-averaging techniquewe quantified the area under thewave signal representative of diastolic flow and normalised this for systolic flow [NDF]. Patients were tilted for 30 minutes [GTN given at 20 minutes] or until presyncope. 18 patients [age 41 ± 15 yrs, 9 females] had tilt-induced presyncope after 21 ± 8minutes. During the last 5 minutes of tilt: BP fell from 98± 12mmHg to 70 ± 18 [p= 0.001]; HR from 82± 12 bpm to 74± 18 [p= 0.09]; MSNA from 47 ± 9 bursts/min to 37 ± 13 [p= 0.04] and NDF from 0.92 units to 0.75 [p= 0.02]. Despite a fall in MSNA during presyncope, active vasoconstriction is maintained in the splanchnic arterioles resulting in decreased diastolic blood flow. Stroke volume falls at this time, therefore a relative increase in systolic flow is not contributing to the fall in NDF. The dominant hypotensive mechanism in vasovagal syncope is likely to be splanchnic venous pooling which occurs despite decreased arterial inflow. doi:10.1016/j.autneu.2015.07.264 Symposium 4: Is renal nerve ablation a sound therapeutic strategy for the clinical treatment of hypertension? Insights gleaned from recent studies 4.1 Role of afferent and efferent renal nerves inmediating cardiovascular responses to renal denervation in experimental hypertension

Cerebral Flow Velocities During Daily Activities Depend on Blood Pressure in Patients With Chronic Ischemic Infarctions

Target blood pressure (BP) values for optimal cerebral perfusion after an ischemic stroke are still debated. We sought to examine the relationship between BP and cerebral blood flow velocities (BFVs) during daily activities. We studied 43 patients with chronic large vessel ischemic infarctions in the middle cerebral artery territory (aged 64.2+/-8.94 years; at 6.1+/-4.9 years after stroke) and 67 age-matched control subjects. BFVs in middle cerebral arteries were measured during supine baseline, sitting, standing, and tilt. A regression analysis and a dynamic phase analysis were used to quantify the BP-BFV relationship. The mean arterial pressure was similar between the groups (89+/-15 mm Hg). Baseline BFVs were lower by approximately 30% in the patients with stroke compared with the control subjects (P=0.0001). BFV declined further with postural changes and remained lower in the stroke group during sitting (P=0.003), standing (P=0.003), and tilt (P=0.002) as compared with the control group. Average BFVs on the stroke side were positively correlated with BP during baseline (R=0.54, P=0.0022, the slope 0.46 cm/s/mm Hg) and tilt (R=0.52, P=0.0028, the slope 0.40 cm/s/mm Hg). Regression analysis suggested that BFV may increase approximately 30% to 50% at mean BP >100 mm Hg. Orthostatic hypotension during the first minute of tilt or standing was independently associated with lower BFV on the stroke side (P=0.0008). Baseline BP-BFV phase shift derived from the phase analysis was smaller on the stroke side (P=0.0006). We found that BFVs are lower in patients with stroke and daily activities such as standing could induce hypoperfusion. BFVs increase with mean arterial pressure >100 mm Hg. Dependency of BFV on arterial pressure may have implications for BP management after stroke. Further prospective investigations are needed to determine the impact of these findings on functional recovery and strategies to improve perfusion pressure during daily activities after ischemic stroke.

Transient influence of end-tidal carbon dioxide tension on the postural restraint in cerebral perfusion

In the upright position, cerebral blood flow is reduced, maybe because arterial carbon dioxide partial pressure (Pa(CO(2))) decreases. We evaluated the time-dependent influence of a reduction in Pa(CO(2)), as indicated by the end-tidal Pco(2) tension (Pet(CO(2))), on cerebral perfusion during head-up tilt. Mean arterial pressure, cardiac output, middle cerebral artery mean flow velocity (MCA V(mean)), and dynamic cerebral autoregulation at supine rest and 70 degrees head-up tilt were determined during free breathing and with Pet(CO(2)) clamped to the supine level. The postural changes in central hemodynamic variables were equivalent, and the cerebrovascular autoregulatory capacity was not significantly affected by tilt or by clamping Pet(CO(2)). In the first minute of tilt, the decline in MCA V(mean) (10 +/- 4 vs. 3 +/- 4 cm/s; mean +/- SE; P < 0.05) and Pet(CO(2)) (6.8 +/- 4.3 vs. 1.7 +/- 1.6 Torr; P < 0.05) was larger during spontaneous breathing than during isocapnic tilt. However, after 2 min in the head-up position, the reduction in MCA V(mean) was similar (7 +/- 5 vs. 6 +/- 3 cm/s), although the spontaneous decline in Pet(CO(2)) was maintained (P < 0.05 vs. isocapnic tilt). These results suggest that the potential contribution of Pa(CO(2)) to the postural reduction in MCA V(mean) is transient, leaving the mechanisms for the sustained restrain in MCA V(mean) to be identified.

Hemodynamic Parameters and Heart Rate Variability during a Tilt Test in Relation to Gene Polymorphism of Renin‐Angiotensin and Serotonin System

The aim of the study was to evaluate the renin-angiotensin system and serotonin transporter gene polymorphisms in relation to hemodynamic parameters and heart rate variability during a head-up tilt test (HUT) in patients with vasovagal syncope. DNA was collected from 191 patients (mean age 44+/-18 years, 61 men, 130 women). The following gene polymorphisms were determined in genomic DNA: angiotensin-converting enzyme insertion/deletion polymorphism (I/D ACE), angiotensinogen gene polymorphism (M 235), angiotensin II receptor type 1 (ATR1) polymorphism (A 11666C), and polymorphism of serotonin transporter gene (5HTTLPR).Heart rate variability during HUT was assessed in 5-minute intervals by low frequency, high frequency, standard deviation of the normal-to-normal (SDNN), and root mean square successive difference parameters. AA genotype of A 1166C polymorphism was associated with lower minimal systolic blood pressure (SBP) and diastolic blood pressure (DBP) during HUT compared with other genotypes (minimal SBP: AA 59.6+/-21,8, AC 79.9+/-22.7, CC 65.4+/-22.7 mmHg, P=0.007), (minimal DBP: AA 36.4+/-22.7, AC 52.3+/-22.9, CC 45.4+/-19.5 mmHg, P=0.007).AA genotype was also associated with higher SDNN compared to other genotypes in the early phase of HUT (SDNN in 5 minutes of tilt: AA 59.7+/-24.6, AC 50.6+/-20.6, CC 46.0+/-13.2, P=0.01) and at syncope occurrence (SDNN: AA 71.0+/-20.9, AC 58.2+/-17.9, CC 58+/-10, P=0.04) AA genotype of A 1166C polymorphism in the ATR1 gene may be associated with hypotension and decline in sympathetic tone during HUT. Its role in genetic predisposition to vasovagal syncope cannot be excluded.

Comparative effects of ivabradine, a selective heart rate‐lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise

To compare in humans the effects of ivabradine and propranolol on cardiac and systemic haemodynamics at rest, during tilt and exercise. Nine healthy volunteers randomly received single oral doses of ivabradine (Iva, 30 mg), propranolol (Propra, 40 mg) or placebo (Plac) during a double-blind cross-over study. Doses were selected to be equipotent in heart rate (HR) reduction. HR, systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI, bioimpedance), rate pressure product (RPP), plasma epinephrine (E) and norepinephrine (NE), were measured at rest at baseline, before and after two tilt and exercise tests, started 2 and 5 h after drug intake. Heart rate variability (low to high frequency ratio LF/HF) was evaluated at rest and at 5 th minute of tilt. At rest, HR and RPP decreased similarly with Iva and Propra (both P < 0.01). During tilt, HR increased less with Iva than Propra (P < 0.01), LF/HF decreased after Iva (P < 0.03), SBP and mean blood pressure decreased after Propra (both P < 0.01), RPP decreased similarly after Iva and Propra (both P < 0.01) and CI decreased to a greater extent with Propra than with Iva or Plac (both P < 0.04). During exercise, Iva and Propra similarly decreased HR (both P < 0.01) and RPP (P < 0.01). These results demonstrate that for a similar decrease in HR at rest and during sympathetic stimulation, acute administration of ivabradine, a selective heart rate-lowering agent, decreased myocardial oxygen demand to the same extent as a reference beta-blocker, propranolol, but without evidence of depressant effect on cardiac function.

Enhanced plasma catecholamine and cAMP response during the head-up tilt test in patients with vasovagal syncope

Vasovagal syncope appears related to transient changes in sympathetic neural outflow. Several studies have documented sympathetic inhibition at the time of syncope. However, data on the activity of the sympathetic nervous system a short time before the onset of syncope are controversial. The aim of the study was to examine sympathoadrenal activity by measuring levels of plasma catecholamines and plasma cAMP in patients with vasovagal syncope induced in the head-up tilt test (HUT). Sixty-one syncopal patients (age 35 +/- 15 years) underwent the passive HUT (60 degrees, 45 minutes). Blood samples for measurement of noradrenaline (NA), adrenaline (A) and dopamine (D) were obtained prior to tilt (0 minutes), at 5 minutes of tilt and at syncope or at the end of the HUT (45 minutes). Two samples were obtained for measurement of cAMP: at 0 minutes and at the end of the test. Plasma levels of NA, A and D were measured using high-performance liquid chromatography; plasma cAMP was measured using a radioimmunoassay technique. Thirty-three patients (15 men, age 35 +/- 16 years) developed vasovagal syncope during the test (HUT-positive); twenty-eight patients (15 men, age 34 +/- 14 years) completed the test without syncope (HUT-negative). No significant differences in NA, A and D were observed between the two groups at baseline or at 5 minutes of tilt. At the time of syncope, catecholamine levels in HUT-positive patients were higher than baseline levels (NA 428 vs. 209 pg/ml, A 90 vs. 55 pg/ml, D 297 vs. 142 pg/ml) and higher than in HUT-negative patients (NA 428 vs. 263 pg/ml, A 98 vs. 67 pg/ml, D 297 vs. 195 pg/ml). cAMP levels increased at syncope and were higher than in non-syncopal patients at the end of the HUT (607 +/- 460 vs. 328 +/- 297 nmol/ml). Vasovagal syncope induced by tilt testing is associated with increased levels of noradrenaline, adrenaline, dopamine and cAMP. These results suggest that sympathoadrenal activation antecedes development of vasovagal syncope and may play a role in its pathophysiology.

Comparison of hemodynamic adaptation to orthostatic stress in patients with hypertrophic cardiomyopathy with or without syncope and in vasovagal syncope

This study was designed to investigate whether, in patients with hypertrophic cardiomyopathy (HC), tilt-induced volume unloading triggers a peripheral reflex similar to that seen in patients with a history of vasovagal syncope or rather acts through an intrinsic cardiac mechanism secondary to diastolic dysfunction. Thirty-seven patients with HC (10 with and 27 without a history of syncope), 10 patients with vasovagal syncope, and 9 controls underwent 70° head-up tilt for 45 minutes during continuous radionuclide monitoring of left ventricular function. We focused on the initial 5 minutes into the tilt test, well before symptoms occurred, to exclude that the observed hemodynamic changes were the consequence rather than the cause of syncope. HC patients with previous syncope and vasovagal patients experienced significant hypotension after the initial 5 minutes of tilt. Only HC patients with a history of syncope had a significant decrease in cardiac output, which began at the initial stage of the test. Systemic vascular resistance decreased in vasovagal patients, but increased in the HC syncopal group. Baseline peak filling rate was lower (2.4 ± 0.5 vs 3.3 ± 1.1 stroke counts/s, p = 0.03) and a “pseudonormal” or a restrictive pattern of left ventricular filling was more frequent (70% vs 26%, p = 0.02) in HC patients with than without a history of syncope. Thus, significant hypotension or frank syncope during orthostatic stress in HC patients with a history of syncope is due to an early decrease in cardiac output, which occurs well before the onset of symptoms; such impaired hemodynamic adaptation seems to be related to diastolic dysfunction.

Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope.

The importance of cardiac output (CO) to blood pressure level during vasovagal syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients, CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min, respectively. In TS patients, CO decreased during the first minute (from 3.3 +/- 0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001) than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in CO may contribute to hypotension some minutes before syncope occurs.

Genetic analysis of blood pressure and blood pressure response to orthostatic stress: are the same genes involded in both traits?

P20 Aim: Our aim was to investigate genetic involvement in systolic and diastolic blood pressure (SBP and DBP) responses to orthostatic stress.Methods: Data from 453 members of 4 large kindreds, each ascertained through a white male with essential hypertension, were used. Blood pressures were measured seated, supine (SBP mean = 111mmHg and DBP mean = 68 mmHg), and at 1-, 2- and 3- minutes of 70-degree head-up tilt. A variance components analytical approach implemented in the SOLAR statistical genetic analytical package was used. Sex, age and age squared were covariates in all of the models. Bivariate analyses were conducted to examine pleiotropy between supine blood pressures with those at 1-, 2-, and 3-minutes of tilt. Likelihood ratio tests were used to evaluate different genetic models. Results: For SBP the covariates explained 10 to 15 percent of the phenotypic variance. Significant heritabilities were observed for seated and supine blood pressures; e.g., 0.29 and 0.31 respectively for SBP. Blood pressures resulting from the baroreceptor reflex response to arterial pressure change induced by tilt had comparable heritabilities; e.g., at 1-, 2- and 3-minutes post-tilt they were 0.24, 0.29, and 0.36, respectively for SPB. Similarly, the blood pressure response, the change in blood pressure from supine to tilt, had modest heritabilities of 0.08 (n.s.), 0.16, and 0.19 respectively for SBP, and 0.13, 0.08 (n.s.), and 0.16 for DBP. For both SBP and DBP, the bivariate models testing for pleotropy between the supine pressure and the pressure at each minute of tilt showed that there was no evidence for differential gene expression for blood pressure in these two conditions. Conclusions: Resting levels of blood pressure, the levels reached in response to orthostatic stress, and the actual change in blood pressure resulting from that stress are heritable. The genes that are involved in establishing the control of resting supine blood pressure do not differ from those that are involved in mediating the first 3 minutes of blood pressure response to an orthostatic stress of 70-degree head-up tilt (i.e., there is complete pleiotropy for these traits).

Oscillatory patterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus.

We tested the hypothesis that a common oscillatory pattern might characterize the rhythmic discharge of muscle sympathetic nerve activity (MSNA) and the spontaneous variability of heart rate and systolic arterial pressure (SAP) during a physiological increase of sympathetic activity induced by the head-up tilt maneuver. Ten healthy subjects underwent continuous recordings of ECG, intra-arterial pressure, respiratory activity, central venous pressure, and MSNA, both in the recumbent position and during 75 degrees head-up tilt. Venous samplings for catecholamine assessment were obtained at rest and during the fifth minute of tilt. Spectrum and cross-spectrum analyses of R-R interval, SAP, and MSNA variabilities and of respiratory activity provided the low (LF, 0.1 Hz) and high frequency (HF, 0.27 Hz) rhythmic components of each signal and assessed their linear relationships. Compared with the recumbent position, tilt reduced central venous pressure, but blood pressure was unchanged. Heart rate, MSNA, and plasma epinephrine and norepinephrine levels increased, suggesting a marked enhancement of overall sympathetic activity. During tilt, LF(MSNA) increased compared with the level in the supine position; this mirrored similar changes observed in the LF components of R-R interval and SAP variabilities. The increase of LF(MSNA) was proportional to the amount of the sympathetic discharge. The coupling between LF components of MSNA and R-R interval and SAP variabilities was enhanced during tilt compared with rest. During the sympathetic activation induced by tilt, a similar oscillatory pattern based on an increased LF rhythmicity characterized the spontaneous variability of neural sympathetic discharge, R-R interval, and arterial pressure.

Inadequate sympathovagal balance in response to orthostatism in patients with unexplained syncope and a positive head up tilt test

AIMTo analyse the immediate response of heart rate variability (HRV) in response to orthostatic stress in unexplained syncope.SUBJECTS69 subjects, mean (SD) age 42 (18) years, undergoing 60° head up tilt...

Dual chamber pacing for neurally mediated syncope with a prominent cardioinhibitory component.

The role of cardiac pacing for treatment of recurrent neurally mediated syncope (NMS) remains controversial. We hypothesized that dual chamber pacing in NMS patients with a prominent cardioinhibitory component may be beneficial. Twelve patients (mean age = 37.8+/-17 years, range 15-78 years, 7 men and 5 women) with a mean of 4+/-2.2 episodes of syncope underwent tilt table evaluation. Patients were passively tilted to 70 degrees head-up position for 20 minutes and then returned to the supine position. Isoproterenol was then infused at 1-2 microg/min to increase heart rate by > or = 25% and tilt was repeated. Patients lost consciousness after 16+/-6 minutes of tilt; nine patients had syncope in the baseline state and three during isoproterenol infusion. All patients had at least 5 seconds of asystole with a mean of 9.5+/-4 seconds (range 5-20 s). A dual chamber permanent pacemaker with a special feature allowing heart rate acceleration in response to bradycardia was implanted in all patients. During a mean follow-up of 18.6+/-4.2 months, 11 (92%) of these patients were free of syncope and had negative tilt table test. One (8%) patient had two episodes of syncope. We conclude that dual chamber pacing may be beneficial in patients with NMS with a prominent cardioinhibitory component.

Plasma Catecholamines and Cyclic AMP Response During Head‐Up Tilt Test in Patients with Neurocardiogenic (Vasodepressor) Syncope

To examine hemodynamic, plasma catecholamines, and cyclic AMP changes during tilt in patients with neurocardiogenic (vasodepressor) syncope, six patients underwent 80 degrees head-up tilt test for 10 minutes with isoproterenol infusion (1-3 micrograms/min). Venous blood was sampled in the supine position, at 3 minutes of tilt, and at the onset of vasodepressor reaction during tilt. All patients had previous tilt studies in which vasodepressor syncope had been induced reproducibly (mean 3.3 episodes in each patient). Syncope was induced at 6.1 +/- 0.4 minutes of tilt with an infusion of isoproterenol (mean 1.7 +/- 0.3 micrograms/min). Although arterial pressure and heart rate did not change significantly between in the supine position and at 3 minutes of tilt, plasma norepinephrine increased significantly at 3 minutes of tilt (0.44 +/- 0.10 ng/mL; P < 0.05) and at the onset of vasodepressor reaction (0.49 +/- 0.12 ng/mL; P < 0.01) compared to the supine position with isoproterenol (0.34 +/- 0.10 ng/mL). Also, cyclic AMP (cAMP) increased significantly at 3 minutes of tilt (25.3 +/- 2.0 pmol/mL; P < 0.005) and at the onset of vasodepressor reaction (29.6 +/- 1.7 pmol/mL; P < 0.005) compared to the supine position with isoproterenol (20.4 +/- 1.9 pmol/mL). After administration of selective beta 1-blocker, metoprolol (40 mg/day), plasma norepinephrine, and cAMP during tilt did not change significantly compared to baseline tilt. However, metoprolol prevented the syncope in 3 of 6 patients. After administration of beta 1-, beta 2-blocker, propranolol (30 mg/day), cAMP at 3 minutes of tilt decreased significantly compared to the baseline tilt (16.9 +/- 1.4 pmol/mL vs 25.3 +/- 2.0 pmol/mL; P < 0.05) and propranolol prevented the syncope in all six patients. We concluded that the increase of cAMP may play an important role for the induction of vasodepressor reaction in patients with neurocardiogenic (vasodepressor) syncope. The concentration of cAMP showed more sensitive response to vasodepressor reaction than that of norepinephrine.

Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope

The role of autonomic balance during upright tilt in patients with neurally mediated syncope is unclear. To assess the characteristics of autonomic tone during orthostatic stress, 15 patients (mean age 32 years) with recurrent episodes of syncope (≥2) and a positive response to a 30-minute 60 ° upright tilt were compared with the following control groups: (1) 15 patients (mean age 33.5 years) with ≥2 episodes of recurrent syncope and a negative tilt response, and (2) 15 age-and sex-matched healthy volunteers (mean age 34 years) with no previous history of presyncope or syncope. Time domain measurements assessed were mean RR interval, standard deviation of normal RR intervals, and percentage of normal consecutive RR intervals differing by >50 ms. Frequency domain measurements of the lowfrequency (LF) and high-frequency (HF) bands were obtained, and the LF HF ratio was also calculated. All variables were calculated in the supine position and during the first 5 minutes of upright tilt. No significant difference was observed in the time and frequency domain variables in the supine position between control groups with a negative head-up tilt response and the group with a positive response. The percentage of normal consecutive RR intervals differing by >50 ms during the first 5 minutes of head-up tilt was significantly higher in the group with positive tilt tests than in the controls (25 ± 12% vs 7 ± 4%, p < 0.001). Patients with a positive tilt response did not experience equivalent increases in LF power with upright posture as in controls (40% vs 164%, p < 0.0001). HF power was significantly increased in syncope patients with a positive tilt response during the first 5 minutes of head-up tilt (4.6 ± 0.8 beats/min 2/ Hz) compared with the control group (1.1 ± 0.5 beats/min 2/Hz, p < 0.01). An LF HF ratio ≤6 during the first 5 minutes of tilt was highly predictive of syncope occurrence, subsequently noted at 15 ± 6 minutes of tilt (sensitivity 88%, specificity and positive predictive value 100%). Sympathovagal balance during the first 5 minutes of head-up tilt was markedly abnormal in patients with neurally mediated syncope and a positive head-up tilt response. Failure to withdraw parasympathetic tone during upright tilt may play a role in determining susceptibility to recurrent neurally mediated syncope.

Effects of β-adrenergic blockade on vasodepressor reaction in patients with vasodepressor syncope

The mechanism of vasodepressor reaction induced by head-up tilt test in patients with vasodepressor syncope is not clearly understood. We hypothesized that an abnormal alteration of β-adrenergic transmission could be involved in these patients. We measured plasma catecholamine concentration during tilt and density of β-adrenoceptors and tested the effects of β-adrenergic blockers in the prevention of the vasodepressor reaction in patients with vasodepressor syncope. Ten patients had reproducibly induced vasodepressor syncope (mean 3.1 ± 0.3 episodes in each patient) with head-up tilt (80 degrees) for 10 minutes with isoproterenol infusion (1 to 3 μg/min). Syncope occurred at 6.3 ± 1.7 minutes during tilt with isoproterenol infusion. The plasma norepinephrine concentration before administration of β-blocker was significantly elevated during tilt compared to the supine position (0.347 ± 0.079 ng/ml in supine position with isoproterenol vs 0.468 ± 0.082 ng/ml at 3 minutes of tilt, p < 0.001, and vs 0.503 ± 0.106 ng/ ml at the onset of vasodepressor reaction, p < 0.005; n = 8). Plasma norepinephrine after administration of the selective β 1-adrenergic blocker metoprolol (40 mg/day) was similarly elevated (0.282 ± 0.071 ng/ml in supine position with isoproterenol vs 0.390 ± 0.078 ng/ml at 3 minutes of tilt, p < 0.05, n = 6; and vs 0.547 ± 0.152 ng/ml at the onset of vasodepressor reaction, p < 0.001, n = 3). Plasma norepinephrine after administration of the nonselective β-blocker propranolol (30 mg/day) was not significantly elevated (0.254 ± 0.063 ng/ml in supine position with isoproterenol vs 0.339 ± 0.081 ng/ml at 3 minutes of tilt, p not significant; and vs 0.343 ± 0.079 ng/ml at 10 minutes of tilt, p not significant, n = 6). Metoprolol prevented vasodepressor syncope in 5 of 10 patients; propranolol prevented syncope in all 10 patients ( p < 0.05). Heart rate after administration of propranolol did not increase in either the supine position with isoproterenol or during tilt compared to control tilt and tilt after administration of metoprolol. We abserved no significant differences in the number and afrinity of β-adrenoceptors between five patients with vasodepressor syncope and tive age-matched normal subjects. We conclude that propranolol is far more useful for the prevention of vasodepressor syncope than metoprolol. Our data suggest that β 2-adrenergic transmission may play an important role in the induction of vasodepressor reaction in patients with vasodepressor syncope.

Hemodynamic response to orthostatic stress in the elderly with systolic systemic hypertension before and after long-term thiazide therapy

The hemodynamic effects of orthostatic stress in elderly subjects with systolic hypertension were studied before and after long-term hydrochlorothiazide therapy (50 mg daily). Sixteen nondiabetic men aged 70 ± 1 (SE) years participated in the study initially, and 12 completed 1 year of therapy. Patients underwent 45 ° head-up incline on a tilt table before, after 1 month and after 1 year of therapy. Hemodynamic variables were measured in the following situations: (1) the supine position, (2) immediately after completion of passive 45 ° head-up position at 0 minute, (3) at 15 minutes in the tilted state while patients performed intermittent foot movements to minimize gravitational pooling and simulate the standing position outside the laboratory, and (4) after returning to the supine position. Systolic and diastolic blood pressure (BP) decreased significantly after 1 month of therapy, and this reduction was maintained up to 1 year in all aforementioned body positions, with the exception of diastolic BP at 0 minute of tilt, which was significant at 1 year only. Before therapy was begun, there was a significant reduction in systolic BP immediately after completion of fitting; however, this was statistically insignificant both at 1 month and 1 year of therapy. Thus, the data may help dispel the concern of exacerbating the hypotensive response to orthostatic stress in patients with systolic hypertension after long-term thiazide diuretic therapy.

Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia

Susceptibility to transient hypotension-bradycardia of neurally mediated origin has been attributed in part to accentuated afferent neural traffic arising from cardiopulmonary mechanoreceptors, and consequently, may be diminished by agents with anticholinergic and negative inotropic effects, such as disopyramide phosphate. This study assessed electrocardlographic and hemodynamie responses to upright tilt testing (alone or during isoproterenol infusion) before and after disopyramide therapy in 10 patients (age range 16 to 74 years) with recurrent syncopal episodes of neurally mediated origin. Untreated, syncope occurred at ≤7 minutes of tilt alone (6 patients) or tilt plus isoproterenol at ≤3 μg/min (4 patients) and was associated with hypotension (mean arterial pressure, 40 ± 16 mm Hg vs baseline 76 ± 10 mm Hg, p <0.001) and inappropriate heart rate slowing (mean heart rate, 59 ± 39 beats/min vs baseline 88 ± 18 beats/min, p <0.005). After oral disopyramide 150 mg 3 times daily (mean plasma level, 3.0 ± 0.64 μg/ml), all patients tolerated 10 minutes of both tilt and tilt plus isoproterenol (maximum dose, 3 μg/min) without symptoms, hypotension (mean arterial pressure; tilt 1 min, 79 ± 7 min Hg vs tilt 10 min, 77 ± 8 mm Hg, difference not significant) or bradycardia (mean heart rate; tilt 1 min, 81 ± 12 beats/min vs tilt 10 min, 83 ± 11 beats/min, difference not significant). Furthermore, during subsequent 20 ± 5 months of disopyramide therapy, all but 1 patient remain asymptomatic. Thus, oral disopyramide may be effective for preventing inducible and spontaneous neurally mediated syncope.