Effects of central muscarinic-1 receptor stimulation on blood pressure regulation.

Stimulation of central nervous system muscarinic-1 (M1) receptors in animals increases blood pressure, heart rate, and sympathetic outflow. In Alzheimer's disease, stimulation of central M1 receptors is reduced. When the oral formulation of the selective M1 agonist xanomeline was tested for the treatment of Alzheimer's disease, an increased incidence of syncope was observed. Therefore, we used Alzheimer's disease as a model of relative M1 deficiency to determine the effect of M1 receptor stimulation on blood pressure regulation in humans. Eight Alzheimer's patients and 6 healthy age- and sex-matched subjects underwent blood pressure, heart rate, forearm vascular resistance, plasma norepinephrine, and heart rate variability measurements during 90 minutes after ingestion of xanomeline or placebo, then during 45 minutes of head-up tilt. Alzheimer's patients were studied on three occasions: after placebo, the first dose of xanomeline, and 3 days of xanomeline. Normal subjects were studied after placebo and the first dose of xanomeline. A subset of 5 Alzheimer's patients was studied with the peripheral muscarinic antagonist methscopolamine. Oral xanomeline increased supine systolic and diastolic blood pressures in normal subjects and heart rate and plasma norepinephrine in all subjects. During the placebo tilt, 0 of 8 Alzheimer's patients and 2 of 6 healthy subjects developed near-syncope, and during the first-dose xanomeline tilt, 4 of 8 Alzheimer's patients and 3 of 6 healthy subjects had near-syncope. The maximal decrease in systolic blood pressure during tilt was greater with xanomeline than placebo in both groups (P<.03). Methscopolamine did not prevent xanomeline-induced hypotension. Central M1 receptor stimulation with the oral formulation of xanomeline in humans is associated with sympathetic stimulation under supine conditions and impaired baroreflex compensation during tilt. Alzheimer's patients, who presumably lack M1 receptor activity, may have a reduced risk of tilt-induced syncope compared with normal subjects. Both groups, however, have enhanced susceptibility to hypotension and syncope when M1 receptor activity is pharmacologically increased.

Arterial closing pressure correlates with diastolic pseudohypertension in the elderly.

BACKGROUND: Pseudohypertension has frequently been reported in the elderly population, with the diastolic measurement being the most frequent source of error. There is no satisfactory noninvasive method of calculating the error in the blood pressure reading. We investigated the role of arterial closing pressure in the diagnosis of diastolic pseudohypertension. METHODS: Indirect and direct blood pressure were measured in 24 elderly patients. Brachial artery closure was visualized by ultrasound in all subjects. Arterial closing pressure (ACP) was recorded as zero if the vessel was seen to close spontaneously when it was isolated from central arterial pressure. If the vessel did not close spontaneously, a water cuff was applied externally over the artery and the additional pressure required to close it was recorded. RESULTS: Diastolic pseudohypertension was noted in 8 subjects. Spontaneous closure of the brachial artery occurred in the 16 without pseudohypertension; i.e., ACP = 0. Additional pressure of the water cuff (range: 30-158 mm Hg) was required to collapse the artery (ACP) in those with diastolic pseudohypertension. ACP correlated with the extent of diastolic pseudohypertension (range: 5-17 mm Hg); r = .85, p < .001). CONCLUSION: We propose that ACP may be used to diagnose the presence and extent of pseudohypertension.

Withdrawing cardiovascular medications at a syncope clinic.

It is widely assumed in clinical practice that drug treatment associated with hypotension can result in falls and syncope, but there is actually very little evidence to support this. Therefore the data in all patients whose cardiovascular medications were stopped at a falls/syncope clinic were analysed to see if their symptoms were altered and if renewal of these medications was necessary at subsequent visits. Of 338 consecutive referrals, cardiovascular medications had been stopped in 65 (19%). At follow up 78% reported improvement in their original presenting symptoms and renewal of medication was not necessary in 77% off antianginals, 69% off antihypertensives, and 36% off antiarrhythmics. It was concluded that adjusting cardiovascular medications could help in the management of falls and syncope and may obviate the need for other treatment. These medications can be stopped in select patients if there is regular monitoring and this should reduce unwanted side effects and costs of these drugs.

Additional risk factors in atrial fibrillation patients not receiving warfarin.

OBJECTIVE: To study how many elderly inpatients with previously diagnosed atrial fibrillation were not receiving anticoagulant prophylaxis, and the prevalence of additional risk factors in these patients. METHODS: All new admissions to a department of medicine for the elderly were screened for atrial fibrillation. Additional risk factors were analysed in those with established atrial fibrillation who were not receiving warfarin. Previous hospital admissions, documentation of why prophylaxis was not being used and use of aspirin as an alternative agent were also examined. RESULTS: 56 patients had previously diagnosed atrial fibrillation; 82% were not taking warfarin and 71% of these were not on aspirin either. All patients not taking warfarin had one additional risk factor for stroke and 95% had two or more. Fifty-two percent had attended hospital when atrial fibrillation was present within the previous 3 years and there was nothing documented in their records to explain why anticoagulation had not been used. CONCLUSIONS: Most elderly inpatients with established atrial fibrillation were not taking warfarin. All had additional risk factors for stroke, which increase the absolute benefit of anticoagulation.

Angiodysplasia and ileal carcinoid.

A case of angiodysplasia, symptomatic for 18 years, is presented. This case highlights the difficulty of establishing a diagnosis. Associated findings included aortic stenosis and a carcinoid tumour of the ileum. Despite transfusion of a total of 1200 units of blood the liver was normal at necropsy.

Are hydrogen breath tests valid in the elderly?

Hydrogen breath testing (HBT) is frequently used as an alternative to small bowel aspiration in the diagnosis of small intestinal bacterial overgrowth (SIBO). The role of the glucose HBT was assessed in 30 elderly patients. A positive HBT was recorded in 15 of 20 SIBO cases and 7 of 10 culture negatives (sensitivity 75% and specificity 30%). The correlation coefficients between hydrogen gas (H2) rise and total bacterial count (r = 0.21) and H2 rise and anaerobic count (r = 0) were not significant. Fasting H2 levels were raised in only 4 of the 20 SIBO cases. This study indicates that the HBT is not reliable in the diagnosis of SIBO in the elderly. There was no evidence from the data that different H2 levels or bacterial counts would significantly alter the reliability of the HBT. This work suggests that factors other than small bowel bacteria are involved in the production and expiration of H2 in the elderly, and that these factors need to be considered in the interpretation of this breath test.