Caffeine abstinence augments the systolic blood pressure response to adenosine in humans

Blood pressure and heart rate responses to adenosine infusion (35, 70, and 140 microg/kg/min, intravenously) were studied in 7 healthy men after 6, 30, 78, 150, and 318 hours of abstinence from regular caffeine use. The finding that caffeine abstinence augmented the systolic pressor response (from -1 +/- 2 mm Hg at 6 hours to +9 +/- 2 mm Hg at 318 hours; p = 0.01) but not the tachycardic response to adenosine has implications for current clinical and research applications of this purine.     

Postexercise systolic blood pressure response: clinical application to the assessment of ischemic heart disease

Stress test parameters indicating the presence and extent of coronary artery disease have traditionally included such variables as exercise duration, and the blood pressure and ST-segment responses to exercise. The three-minute systolic blood pressure ratio, another important indicator of significant coronary artery disease, is a useful and readily obtainable measure that can be applied in all patients who are undergoing stress testing for the evaluation of known or suspected ischemic heart disease. The ratio is calculated by dividing the systolic blood pressure three minutes into the recovery phase of a treadmill exercise test by the systolic blood pressure at peak exercise. A three-minute systolic blood pressure ratio greater than 0.90 is considered abnormal and has a diagnostic accuracy of approximately 75 percent for the detection of coronary artery disease (i.e., an accuracy comparable to that of ST-segment depression). Higher values for the ratio are associated with more extensive coronary artery disease, as well as an adverse prognosis after myocardial infarction. Thus, the three-minute systolic blood pressure ratio provides information that is complementary to the traditional exercise test parameters for identifying high-risk ischemic heart disease.     

Venous hum of the Cruveilhier-Baumgarten syndrome: response to the Valsalva maneuver

The response of the venous hum of the Cruveilhier-Baumgarten syndrome (CBS) to respiration, the cardiac cycle, and changes in posture is not predictable. The Valsalva maneuver may result in an increase in intensity of the hum rather than a decrease. The Cruveilhier-Baumgarten venous hum (CBH) is virtually diagnostic of portal vein hypertension. It may be mistaken for obscure cardiac murmurs. The Cruveilhier-Baumgarten venous hum, unlike the cervical venous hum (CVH), is never present in normal people.     

Paradoxic response of the murmur of idiopathic hypertrophic subaortic stenosis to the Valsalva maneuver

A case of documented severe idiopathic hypertrophic subaortic stenosis in which the Valsalva maneuver resulted in paradoxic attenuation of the systolic ejection murmur is presented. Such a response should not be considered incompatible with the diagnosis of this disease.     

Diagnostic value of postexercise systolic blood pressure response for detecting coronary artery disease in patients with or without hypertension

To evaluate the diagnostic value of the postexercise systolic blood pressure (SBP) response for detecting and evaluating the presence of coronary artery disease (CAD), treadmill testing was conducted in 130 subjects with normal blood pressure and 51 patients with hypertension, each of whom underwent selective coronary angiography. A total of 48 subjects with normal blood pressure and 27 patients with hypertension had no significant narrowing of the coronary artery (control subjects), whereas 82 subjects with normal blood pressure and 24 patients with hypertension had significant narrowing (patients with CAD). The postexercise SBP response was defined on the basis of the SBP ratio (i.e., the SBP at 3 minutes of recovery divided by that at peak exercise). An SBP ratio that exceeded 0.90 (cutoff point for discriminating control subjects from patients with CAD) was considered to be an abnormal SBP response. In the subjects with normal blood pressure, the abnormal SBP response identified CAD as accurately as did ST-segment depression. In the patients with hypertension, the diagnostic accuracy was increased significantly by combining the abnormal SBP response and ST-segment depression (p < 0.01). The SBP ratio increased with the number of diseased coronary arteries. Ten of the 14 patients with a narrowing of the left main coronary artery had an SBP ratio higher than 1.00. The postexercise SBP response may be useful for detecting CAD in patients with and without hypertension and for evaluating the severity of CAD.     

Reproducibility of the circadian systolic blood pressure variation in the elderly

OBJECTIVES: To establish the reproducibility of the nocturnal systolic blood pressure (SBP) change in elderly subjects and to examine the use of cumulative sums (cusums) analysis in the assessment of circadian SBP variation. SUBJECTS: Forty-two untreated elderly subjects (35 hypertensive, 7 normotensive) of mean age 75.5 years from the hypertension clinic at a large teaching hospital participated in a reproducibility study. METHODS: Twenty-four-hour ambulatory blood pressure monitoring was performed and repeated at a median interval of 2 months (range 2 weeks to 9 months). OUTCOME MEASURES: Reproducibility of circadian SBP variation from fixed time analysis of day-night SBP difference and from cusums-based parameters. RESULTS: Twenty-four-hour SBP values were highly reproducible with a coefficient of variation of 5.8%. However, the day-night SBP difference for fixed time periods was poorly reproducible, with a coefficient of variation > 130%. A substantial proportion of subjects (36-43%) altered their 'dipping status' between visits. The use of cusums analysis improved the reproducibility of measures of circadian SBP change (cusums plot height and maximum circadian variation) with coefficients of variation falling to 40 and 38%, respectively. CONCLUSIONS: The use of fixed time definitions results in poor reproducibility of the circadian SBP change in the elderly, which will lead to regression dilution bias when studying the relationship of circadian SBP variation to outcome measures in hypertension. The notion of dipping and non-dipping circadian blood pressure patterns should be abandoned in favour of more reproducible cusums-based measures of circadian blood pressure variation.     

Doppler-derived pulmonary arterial systolic pressure in patients with known systemic arterial pressures

In the present study, we evaluated Doppler-derived systolic pulmonary artery pressure in 476 hypertensive patients. Clinical interpretation of systolic pulmonary arterial pressure should take into account age, body size, and systolic blood pressure values.     

Left ventricular regional systolic motion in patients with right ventricular pressure overload

The highly reactive and cytotoxic hydroxyl radical (OH) was found by electrochemical detection to be produced in reactions involving hydrogen peroxide (H2O2) and the nitric oxide (NO) donor diethylamine- NO complex. Using aromatic hydroxylation of salicylate as a specific indicator of OH, three salicylate hydroxylation products were identified; catechol, 2,3- and 2,5-dihydroxybenzoic acid. Four additional compounds were detected but not identified. The interactions of H2O2 and NO represent a biologically feasible reaction mechanism that can account for OH-induced damage in cellular environments where transition metal ions are unavailable for participation in the superoxide-mediated Fenton reaction. The ability of the NO/H2O2 complex to generate OH independently of iron or other transition metals provides a new focus for studies concerned with the origin of tissue-specific damage caused by oxygen-derived species.     

Influence of dietary fats upon systolic blood pressure in the rat

Studies were performed to determine whether feeding diets with differing fatty acid content and composition had an influence on systolic blood pressure in the rat. Weanling male rats were fed standard laboratory chow (2.9% fat in total), or synthetic diets (10% fat in total) containing fish oil, butter, coconut oil or corn oil, for 5 weeks. Coconut oil and butter diets were rich in saturated fatty acids, whilst fish oil and corn oil were rich in the n-3 and n-6 unsaturated fatty acids respectively. Systolic blood pressure was measured using an indirect tail-cuff method at the end of the feeding period, and compared to a group of weanling rats. Feeding the different diets did not alter the growth of the rats, so all animals were of similar weights at the time of blood pressure determination. Control (chow fed) animals, at nine weeks of age, had higher systolic blood pressures than the weanling, baseline control group. Fish oil fed rats had similar pressures to the chow fed rats. Corn oil fed rats had significantly lower systolic pressures than the controls. The rats led the diets rich in saturated fatty acids (butter and coconut oil) had significantly higher blood pressures than all other groups. Systolic blood pressure was found to be significantly related to the dietary intakes of saturated and unsaturated fatty acids. The dietary intake of linoleic acid was significantly higher in corn oil fed rats than in other groups. Systolic blood pressure was inversely related to linoleic acid intake. Feeding a diet rich in saturated fatty acids significantly increases blood pressure in the rat. A high intake of n-6 fatty acids, and in particular linoleic acid, appears to have a hypotensive effect. Prenatal exposure of the rats to a maternal low protein diet, abolished the hypertensive effects of the coconut oil diet and the hypotensive effect of the corn oil diet upon young adult females. The intrauterine environment may, therefore, be an important determinant of the effects of these fatty acids on blood pressure in later life.     

Corticospinal direct response to transcranial magnetic stimulation in humans

The corticospinal motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex was investigated in comparison with the direct (D) response to electrical stimulation of the exposed motor cortex from the spinal epidural space in 7 neurologically normal patients during brain tumor surgery. The D response during operation was obtained by transcranial magnetic stimulation of the scalp over the areas of the cerebral motor cortex, the hand or arm areas. The magnetic induced D response showed a conduction velocity of 50.5-72.7 m/sec and was resistant to anesthesia and unaffected by muscle relaxants and tolerant to high frequency (500 Hz) paired magnetic stimulus, and the latencies of magnetic MEPs corresponded to those with direct electrical stimulation. Thus, recordings of the D response by transcranial magnetic stimulation are useful for not only identifying the location of the motor cortex during intracranial surgery but also for non-invasive recording of pyramidal tract activity during extracranial surgery under general anesthesia.     

Extended models of the ventilatory response to sustained isocapnic hypoxia in humans

The purpose of this study was to examine extensions of a model of hypoxic ventilatory decline (HVD) in humans. In the original model (model I) devised by R. Painter, S. Khamnei, and P. Robbins (J. Appl. Physiol. 74: 2007-2015, 1993), HVD is modeled entirely by a modulation of peripheral chemoreflex sensitivity. In the first extension (model II), a more complicated dynamic is used for the change in peripheral chemoreflex sensitivity. In the second extension (model III), HVD is modeled as a combination of both the mechanisms of Painter et al. and a component that is independent of peripheral chemoreflex sensitivity. In all cases, a parallel noise structure was incorporated to describe the stochastic properties of the ventilatory behavior to remove the correlation of the residuals. Data came from six subjects from a study by D.A. Bascom, J.J Pandit, I.D. Clement, and P.A. Robbins (Respir. Physiol. 88: 299-312, 1992). For model II, there was a significant improvement in fit for two out of six subjects. The reasons for this were not entirely clear. For model III, the fit was again significantly improved in two subjects, but in this case the subjects were those who had the most marked undershoot and recovery of ventilation at the relief of hypoxia. In these two subjects, the chemoreflex-independent component contributed approximately 50% to total HVD. In the other four subjects, the chemoreflex-independent component contributed approximately 10% to total HVD. It is concluded that in some subjects, but not in others, there may be a component of HVD that is independent of peripheral chemoreflex sensitivity.     

Postural dysregulation in systolic blood pressure is associated with worsened scoring on neurobehavioral function tests and leukoaraiosis in the older elderly living in a community

BACKGROUND AND PURPOSE: Postural hypotension, which occurs frequently in community-living, apparently healthy elderly adults, is usually asymptomatic. However, the relation between postural changes in blood pressure and quantitative higher cerebral function or silent brain lesions remains unclear. We examined the association of exaggerated postural changes in systolic blood pressure with cognitive and quantitative neurobehavioral functions and with brain lesions on MRI in the community-dwelling older elderly. METHODS: The study population consisted of 334 community-dwelling elderly adults, aged 75 years or older (mean age, 80 years). Postural changes in systolic blood pressure (SBP) were assessed using an autosphygmomanometer (BP-203 I). By the difference between the mean of two measurements of SBP at standing and at supine position (dSBP = SBP at upright-SBP at supine position), we divided the subjects into three groups: (1) 20 subjects with postural hypotension (d-SBP < or = -20 mm Hg), (2) 29 subjects with postural hypertension (dSBP > or = 20 mm Hg), and (3) 285 subjects with postural normotension (20 < dSBP < 20 mm Hg). We defined the former two groups as the postural dysregulation group. Scores in four neurobehavioral function tests (Mini-Mental State Exam. Hasegawa Dementia Scale Revised, computer-assisted visuospatial cognitive performance score, and the Up and Go Test) and activities of daily living were compared among the three groups. Brain lesions on MRI, including number of lacunes and periventricular hyperintense lesions, were compared among 15 age- and sex-matched control subjects with postural hypotension, 15 with postural hypertension, and 30 with postural normotension. RESULTS: Twenty subjects (6.0%) exhibited postural hypotension and 29 (8.7%) postural hypertension. Scores in neurobehavioral functions and activities of daily living were significantly lower in the postural dysregulation group (both postural hypotension and hypertension groups) than in the postural normotension group. The postural dysregulation group exhibited significantly more advanced periventricular hyperintensities than the normotension group. CONCLUSIONS: Asymptomatic community dwelling elderly individuals with postural hypotension as well as those with postural hypertension had poorer scores on neurobehavioral function tests and more advanced leukoaraiosis demonstrated on MRI than those without exaggerated postural changes in SBP.     

Gastric acidity influences the blood response to a beta-carotene dose in humans

The effect of gastric acidity on the blood response to a single dose of 120 mg beta-carotene in humans was investigated in 12 normal subjects (5 women, 7 men) aged 23-68 y. Omeprazole was used for 7 d to obliterate gastric acid secretion and to raise gastric pH to > 4.5. In a crossover design, six subjects were randomly assigned to take beta-carotene with omeprazole either at the beginning (day 9) or at the end (day 26) of the study. The beta-carotene response in blood was not altered by the experimental order. Results from the high-gastric-pH phase (ie, with omeprazole) were analyzed together and compared with the results from the low-gastric-pH phase (ie, without omeprazole). The increases of serum concentrations of both trans beta-carotene and cis beta-carotene 6 and 24 h after the beta-carotene dose were significantly greater at a low gastric pH (pH = 1.3 +/- 0.1, ie, without omeprazole) than those at a high gastric pH (pH = 6.4 +/- 0.3, ie, with omeprazole), P < 0.02. Similarly, 24 h after beta-carotene administration, the area under the blood beta-carotene response curve (trans plus cis beta-carotene) was significantly greater at a low gastric pH (6825 +/- 760 nmol.h/L) than at a high gastric pH (3390 +/- 550 nmol.h/L), P < 0.002. In investigations of bacterial overgrowth, gelatin capsule disintegration and isomeric profiles associated with high and low pH, we could not identify factors to explain the differences observed in the blood response curves between low-gastric-pH and high-gastric-pH conditions. A suppressed blood response of beta-carotene at a high intraluminal pH may have been due to the slower movement of negatively charged micelles through the unstirred water layer and cell membrane.     

Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans

Vascular endothelin-receptor stimulation results in vasoconstriction and concomitant production of the vasodilators prostaglandin I2 and nitric oxide. The vascular effects of cyclooxygenase (COx) blockade (diclofenac intravenously) and the subsequent vasoconstrictor response to endothelin-1 (ET-1) infusion 30 min after diclofenac were studied in healthy men. With COx blockade, cardiac output (7%) and splanchnic (14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flow returned to basal value within 30 min. Mean arterial blood pressure increased (4%, P < 0.001). Splanchnic glucose output fell (22%, P < 0.01). Subsequent ET-1 infusion caused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res. Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin. Physiol. (Colch.) 13: 653-662, 1993), the same increase in mean arterial blood pressure (4%), decreases in cardiac output (13%) and splanchnic blood flow (38%), but no significant change in splanchnic glucose output. Renal blood flow reduction was potentiated (33 +/- 3 vs. 23 +/- 2%, P < 0.02), with a total reduction corresponding to 43 +/- 3% (P < 0.01 vs. 23 +/- 3%). We conclude that COx inhibition induces renal and splanchnic vasoconstriction. The selectively increased renal vascular responsiveness to ET-1 emphasizes the importance of endogenous arachidonic acid metabolites (i.e., prostaglandin I2) to counteract ET-1-mediated renal vasoconstriction.     

Treatment with ramipril improves systolic function even in patients with mild systolic dysfunction and symptoms of heart failure after acute myocardial infarction

BACKGROUND: Clinical signs of heart failure such as pulmonary rales and dyspnea, ventricular dysfunction, and ventricular arrhythmia are independent predictors of a poor prognosis after acute myocardial infarction (AMI). HYPOTHESIS: The study aimed to assess the effect of ramipril treatment on mildly depressed left ventricular (LV) systolic function, assessed by atrioventricular (AV) plane displacement in patients with congestive heart failure after AMI. METHODS: The study was a substudy in the Acute Infarction Ramipril Efficacy Study, a double-blind, randomized, place-bo-controlled trial of ramipril versus placebo in patients with symptoms of heart failure after AMI. In all, 56 patients were included in the main study, 4 refused to participate in the substudy, and 4 were excluded for logistical reasons. Echocardiography was performed at entry and after 6 months. Patients who underwent coronary artery bypass grafting during the follow-up period were excluded. RESULTS: At baseline, the patients had modest LV dysfunction, and mean AV plane displacement of 9.7 mm. During follow-up, AV plane displacement increased in ramipril-treated patients from 9.5 to 10.9 mm (p < 0.01). No statistically significant changes were seen in the placebo group. CONCLUSIONS: Ramipril improves LV systolic function in patients with clinical signs of heart failure and only modest systolic dysfunction after AMI. Measurement of AV plane displacement is a simple and reproducible method for detection of small changes in systolic function and may be used instead of ejection fraction in patients with poor image quality.     

Catecholamines contribute to exertional dyspnoea and to the ventilatory response to exercise in normal humans

BACKGROUND: Exogenous catecholamine administration in humans stimulates ventilation. The present study was designed to investigate whether increased endogenous catecholamine release influences objective measures of ventilation and subjective measures of breathlessness in normal subjects. METHODS: Yohimbine, a pre-synaptic alpha 2 adrenoceptor antagonist, or placebo was administered to 10 normal male subjects in a double-blind cross-over fashion. Ventilation and metabolic gas exchange were measured during steady state exercise at 60% of previously determined maximal oxygen consumption. Venous lactate and noradrenaline were measured during exercise. Subjects' sensation of breathlessness and fatigue were recorded using visual analogue scales. RESULTS: Plasma noradrenaline was higher following yohimbine administration (at 6 min exercise; 4.58 +/- 0.56 nmol.l-1 vs 8.74 +/- 1.53; P < 0.05). Oxygen consumption was unchanged, but ventilation was greater throughout exercise following yohimbine. The sensation of exertion was greater following yohimbine, and at any given level of ventilation, the sensation of exertion was greater. CONCLUSIONS: Yohimbine administration causes increased noradrenaline release. This is associated with an increased ventilatory response and an increase in the sensation of exertion during steady state exercise. An increase in circulating noradrenaline might be a mechanism for both increased ventilation and pathological conditions of breathlessness such as chronic heart failure.