Biomedical subjects

J S Floras

Publications and source records attributed to J S Floras.

At least 37 records · Page 2Linked to original sources

PubMed2001

Insulin-mediated blood flow and glucose uptake.

Normal aging is characterized by resistance to insulin-mediated vasodilation and glucose uptake. The mechanism or mechanisms responsible for resistance to the actions of insulin remain unclear. The majority of insulin-mediated glucose uptake occurs in skeletal muscle. It has recently been demonstrated that insulin increases skeletal muscle blood flow via an endothelium-derived, nitric oxide-dependent mechanism. The authors' investigations of the relation between skeletal muscle blood flow and insulin-mediated glucose uptake in healthy elderly and young subjects are reviewed.

Adult↗

PubMed2001

Rationale and design of the Canadian Continuous Positive Airway Pressure Trial for Congestive Heart Failure patients with Central Sleep Apnea--CANPAP.

BACKGROUND: Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is commonly observed in patients with congestive heart failure (CHF), in which it is an independent risk factor for death. Treating CSR-CSA may, therefore, improve outcomes in patients with CHF. OBJECTIVE: The Canadian Continuous Positive Airway Pressure Trial for Congestive Heart Failure Patients with Central Sleep Apnea (CANPAP) is a multicentre, randomized, controlled clinical trial designed to test the hypothesis that treating CSR-CSA with continuous positive airway pressure (CPAP) will reduce the combined rate of all-cause mortality and cardiac transplantation in patients with CHF. Secondary outcomes include the severity of CSR-CSA, left ventricular volumes and function, submaximal exercise capacity, quality of life and hospital admissions. PATIENTS AND METHODS: The aim is to enroll 408 patients with CHF (New York Heart Association class II to IV and left ventricular ejection fraction of less than 40%) and CSR-CSA over a five-year period. Patients are randomly assigned to either standard medical therapy for CHF or standard medical therapy plus CPAP. The trial has 80% power to detect a 35% between-group treatment difference for the all-cause mortality-cardiac transplantation rate. Substudies will assess the role of oximetry as a screening tool for detecting CSR-CSA in patients with CHF, and the effects of CPAP on cardiac arrhythmias and plasma concentrations of natriuretic peptides and catecholamines. CONCLUSIONS: The CANPAP trial will help to define the role of CPAP better as a nonpharmacological intervention for the treatment of patients with CHF who have CSR-CSA.

Canada↗

PubMed2000

Reducing cardiac filling pressure lowers norepinephrine spillover in patients with chronic heart failure.

BACKGROUND: We studied the cardiac sympathetic response to selective unloading of cardiopulmonary baroreceptors in subjects with normal left ventricular (LV) function and congestive heart failure (CHF). METHODS AND RESULTS: Eight patients with normal LV function (age 57+/-5 years, ejection fraction 58+/-2%) and 8 patients with CHF (age 60+/-2 years; ejection fraction 19+/-2%) were studied. Instrumentation consisted of an arterial line, a pulmonary artery catheter, and a coronary sinus thermodilution catheter. The radiotracer technique was used for measurement of cardiac norepinephrine spillover (CANESP) and total-body norepinephrine spillover. Lower-body negative pressure (LBNP) was applied at 2 levels: nonhypotensive and hypotensive LBNP. Nonhypotensive LBNP reduced filling pressures significantly in both groups. Arterial pressure did not change. This reduction in filling pressures caused a significant reduction in CANESP in the CHF group (from 167+/-53 to 125+/-37 pmol/min, P<0.05) but no change in the normal LV function group. Hypotensive LBNP caused a significant increase in CANESP in the normal group (73+/-13 vs 122+/-27 pmol/min, P<0.05) but no significant change in those with CHF. CONCLUSIONS: We conclude that selective reduction in filling pressures lowers cardiac norepinephrine spillover in patients with CHF. These findings suggest that a goal of CHF management should be to reduce cardiac filling pressures while avoiding systemic hypotension.

Heart Failure↗

PubMed2000

Lack of effect of sodium nitroprusside on insulin-mediated blood flow and glucose disposal in the elderly.

Insulin increases skeletal muscle blood flow in healthy young subjects by a nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may contribute to the insulin resistance of normal aging, a state characterized by reduced endothelial production of NO, an attenuated effect of insulin on skeletal muscle blood flow, and resistance to insulin-mediated glucose uptake (IMGU). We tested the hypothesis that the NO donor sodium nitroprusside (SNP) would augment insulin-mediated vasodilation and thus increase IMGU in healthy elderly subjects. Experiments were performed with young (n = 9; age, 25 +/- 1 years; body mass index [BMI], 24 +/- 1 kg/m2) and old (n = 10; age, 78 +/- 2 years; BMI, 25 +/- 1 kg/m2) healthy subjects. Each group underwent two studies in random order. In one study (control), insulin was infused using the euglycemic clamp protocol for 240 minutes at a rate of 40 mU/m2/min (young) and 34 mU/m2/min (old). In the other study (SNP), SNP was coinfused with insulin from 120 to 240 minutes. At regular intervals in each study, blood samples were obtained and calf blood flow was measured using venous occlusion plethysmography. Glucose and insulin values were similar in control and SNP studies in both age groups. In the young, SNP had no effect on blood flow to the calf, but its action in calf resistance vessels augmented insulin-mediated vasodilation, since incremental calf vascular conductance was greater during SNP infusion (control v SNP, 0.027 +/- 0.002 v 0.040 +/- 0.008 mL/100 mL/min/mm Hg, P< .0001). However, SNP had no effect on insulin-mediated glucose disposal. In the elderly, SNP reduced the blood flow to the calf, but this was countered by its effect on calf resistance vessels such that vascular conductance was unaffected (control v SNP, 0.012 +/- 0.003 v 0.011 +/- 0.003 mL/100 mL/min/mm Hg, P = nonsignificant [NS]). Steady-state (180 to 240 minutes) glucose disposal (control v SNP, 7.47 +/- 0.47 v 6.54 +/- 0.56 mg/kg/min, P < .01) rates were significantly lower during SNP infusion. In summary, systemic infusion of SNP did not increase insulin-mediated glucose disposal in either young or old subjects. Thus, the present findings do not support the concept that increasing NO availability will enhance glucose disposal in either age group. However, because the incremental increases in IMGU during SNP infusion paralleled the changes in blood supply to the calf rather than calf vascular conductance, any potential benefits on NO delivery in elderly subjects may have been offset by the direct or reflex effects of systemic hypotension. Other stimuli to NO production that do not cause hypotension must be tested before this therapeutic strategy can be considered as a potential means for enhancing the metabolic actions of insulin in the elderly.

Adult↗

PubMed2000

Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea.

OBJECTIVES: To determine the acute effects of continuous positive airway pressure (CPAP) on baroreceptor reflex sensitivity (BRS) for heart rate during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). DESIGN AND METHODS: In eight CHF patients with OSA not previously treated with CPAP, spontaneous BRS was assessed during overnight polysomnography prior to the onset of sleep, and during stage 2 non-rapid eye movement sleep (NREM) before, during and after application of CPAP. RESULTS: CPAP alleviated OSA and acutely increased the slope of BRS (median, 25%,75%) [from 3.9 (3.5, 4.8) to 6.2 (4.6, 26.2) ms/mmHg, P<0.05]. Increases in the slope of BRS persisted following withdrawal of CPAP [4.9 (4.3, 6.9) ms/mmHg, P<0.05]. CPAP also lowered heart rate (from 81.3 +/- 4.9 to 76.0 +/- 5.7 bpm, P< 0.05), an effect which persisted after its withdrawal (76.7 +/- 5.7 bpm, P < 0.05). Systolic blood pressure at the midpoint of the pressure range of BRS sequences fell while on CPAP (from 139 +/- 8 to 120 +/- 7 mmHg, P < 0.05), and remained lower following CPAP withdrawal (124 +/- 9 mmHg, P < 0.05). CONCLUSIONS: In CHF patients with OSA, CPAP increases acutely BRS during sleep, lowers heart rate and resets the operating point for BRS to a lower blood pressure. These effects of CPAP persist after its withdrawal, suggesting that nocturnal CPAP therapy may cause sustained improvement in the neural control of heart rate.

Adult↗

PubMed2000

Sympathetic responses to atrial natriuretic peptide in patients with congestive heart failure.

Previous studies have shown that atrial natriuretic peptide (ANP) has relative sympathoinhibitory effects that are of potential benefit in patients with congestive heart failure (CHF). In this study, cardiac and systemic sympathetic responses to ANP were evaluated and compared with responses to sodium nitroprusside (SNP) in patients with CHF. Right- and left-heart hemodynamics were obtained simultaneously with cardiac (CANESP) and total body (TBNESP) norepinephrine spillover; these were measured by using the radiotracer technique. Reductions in arterial blood pressure and cardiac filling pressures were similar with both drugs. ANP and SNP caused a significant and similar increase in TBNESP. Mean values for CANESP did not change in either group, but the response of individual patients was dependent on the effect on diastolic blood pressure (r = -0.71, p<0.01). These results do not provide evidence for a sympathoinhibitory effect of ANP, but suggest that in patients with CHF, cardiac sympathoexcitatory response to arterial baroreceptor unloading may be countered by a potential sympathoinhibitory effect caused by a reduction in cardiac filling pressures. In the setting of CHF, vasodilator therapy may decrease cardiac sympathetic activity if systemic hypotension is avoided.

Atrial Natriuretic Factor↗

PubMed2000

Comparison of two indices for forearm noradrenaline release in humans.

Although there is as yet no method which measures directly the neuronal release of noradrenaline in humans in vivo, the isotope dilution technique with [(3)H]noradrenaline has been applied to estimate forearm neuronal noradrenaline release into plasma. Two different equations have been developed for this purpose: one to estimate the spillover of noradrenaline into the venous effluent, and a modified formula (often referred to as the appearance rate) which may reflect more closely changes in the neuronal release of noradrenaline into the synaptic cleft, particularly during interventions that alter forearm blood flow. The present study was performed to compare the effects of two interventions known to exert contrasting actions on neuronal forearm noradrenaline release and forearm blood flow. Intra-arterial infusion of sodium nitroprusside at doses without systemic effect increases forearm blood flow, but not neuronal noradrenaline release. In contrast, lower-body negative pressure at -25 mm Hg causes forearm vasoconstriction by stimulating neuronal noradrenaline release. During sodium nitroprusside infusion, forearm noradrenaline spillover increased from 1.1+/-0.3 to 2.2+/-1.0 pmol x min(-1) x 100 ml(-1) (P<0.05), whereas the forearm noradrenaline appearance rate was unchanged. Lower-body negative pressure did not affect the forearm noradrenaline spillover rate, but increased the forearm noradrenaline appearance rate from 3.4+/-0.4 pmol x min(-1) x 100 ml(-1) at baseline to 5.0+/-0.9 pmol x min(-1) x 100 ml(-1) (P<0.05). These results indicate that the noradrenaline appearance rate provides the better approximation of changes in forearm neuronal noradrenaline release in response to stimuli which alter local blood flow.

Adult↗

PubMed1999

Effect of atrial natriuretic peptide on muscle sympathetic activity and its reflex control in human heart failure.

BACKGROUND: The purpose of this study was to determine if atrial natriuretic peptide (ANP) exerts a relative inhibitory effect on muscle sympathetic nerve activity (MSNA) at rest and during nonhypotensive lower body negative pressure (LBNP) in heart failure, as in healthy subjects. METHODS AND RESULTS: Fifteen men (age 39+/-2 years [mean+/-SE]) with dilated cardiomyopathy (ejection fraction 18+/-3%) received intravenous ANP (50 microgram bolus, then 50 ng. kg-1. min-1) and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. During each infusion MSNA, blood pressure (BP), central venous pressure (CVP), and heart rate (HR) were recorded before and during LBNP at -6 and -12 mm Hg. NTG and ANP caused similar and significant reductions in CVP and diastolic BP, but resting MSNA did not increase with either infusion. LBNP at -6 mm Hg lowered CVP (P<0.05), whereas LBNP at -12 mm Hg caused significant reductions in CVP, systolic BP, and diastolic BP. These effects of nonhypotensive and hypotensive LBNP on CVP and BP were similar during ANP and NTG infusions, yet MSNA was lower both before and with LBNP during ANP (P<0.02). Nonhypotensive LBNP increased MSNA during NTG (+133+/-68 Units; P<0.001) but not during ANP infusion (+24+/-23 Units; P=NS). CONCLUSIONS: These observations are consistent with the concept that ANP exerts a sympathoinhibitory action in heart failure. This is most evident in response to reductions in atrial pressures that do not affect systemic BP.

Adult↗

PubMed1999

Baroreflex sensitivity and the blood pressure response to beta-blockade.

The objective of this analysis was to determine whether changes in baroreflex sensitivity (BRS) within 35 hypertensive patients (25 M, 10 F, mean age 47 years) treated with beta-blockade as monotherapy relate to reductions in ambulatory blood pressure (BP) or its variability. BP was recorded intra-arterially directly from the brachial artery before and during submaximal exercise. BRS was determined by the phenylephrine injection technique. MAP and its variability were determined for the awake period of 24-h BP monitoring. Subjects were randomised to one of atenolol, metoprolol, pindolol, or propranolol, and restudied after a mean of 5 months. Beta-blockade increased BRS in 24 patients and decreased BRS in 11. BRS increased from 6.53+/-4.94 to 9.40+/-8.62 ms/mm Hg (mean +/- s.d.) (P<0.01). Waking ambulatory MAP decreased from 125.8+/-15.8 to 106.4+/-16.2 mm Hg (P<0.0001), but its variability did not change. Higher BRS after chronic beta-blockade was associated with a decrease in waking ambulatory MAP (r = -0.55, P<0.001), but not with its variability (r = -0.08). Beta-blockade attenuated the pressor response to exercise, but there was a positive relationship between the effect of beta-blockade on BRS, and on the rise in systolic BP during bicycling (r = 0.63; P<0.001). Any dampening effect of beta-blockade on BP variability at rest in hypertensive patients with the greatest increase in BRS may be offset by increased pressor responses to physical activity such as exercise. Consequently, BP variability is unaffected, even though reductions in ambulatory BP during chronic beta-blockade are inversely related to changes in BRS. BP responses to beta-blockade may be a function of the action of this class of drugs on BRS. However, there is considerable variation, between subjects, in their effect on BRS. This may have implications for other conditions, such as dilated cardiomyopathy, or following myocardial infarction, in which improvement in BRS is one mechanism by which beta-adrenoceptor blockade could improve survival.

Adolescent↗

PubMed1999

Resting muscle sympathetic nerve activity and peak oxygen uptake in heart failure and normal subjects.

AIMS: Exercise intolerance and increased efferent vasoconstrictor traffic to muscle are two characteristics of heart failure that have not been explicitly linked. We tested the hypothesis that peak oxygen consumption is inversely related to resting muscle sympathetic nerve activity in heart failure. METHODS AND RESULTS: We recorded peroneal muscle sympathetic nerve activity in 17 treated heart failure patients (16 men,1 woman; mean ejection fraction of 26. 0+/-3.2% (SE)) and 17 age-matched healthy subjects (16 men, 1 woman). Oxygen consumption was measured during cycle ergometry to maximal effort. In heart failure and normal subjects, mean peak oxygen consumption was 20.6+/-1.7 vs 32.2+/-2.6 ml x kg-1 x min-1(P<0.0001) and mean muscle sympathetic activity was 49.3+/-2.8 vs 33.0+/-3.3 bursts x min-1(P<.0007) respectively. When age was accounted for by multiple regression analysis, there was a significant relationship between peak oxygen consumption and burst frequency in heart failure (P<0.02) but not in healthy subjects. The percent of predicted peak oxygen consumption achieved (based on age, sex and body size) was inversely related to muscle sympathetic nerve burst frequency in heart failure (r=-0.71, P<0.0014) but not in normal subjects (r=-0. 44, P<0.08;P<0.0001 for this comparison). CONCLUSION: Reduced exercise capacity in heart failure is related to increased efferent sympathetic traffic to calf muscle. These observations are consistent with the concept of a peripheral neurogenic limit to exercise in heart failure.

Adult↗

PubMed1999

Entrainment of blood pressure and heart rate oscillations by periodic breathing.

Cheyne-Stokes respiration (CSR) is a form of periodic breathing associated with periodic oscillations in blood pressure (BP) and heart rate (HR), which have been attributed to hypoxia and arousals from sleep. We hypothesized that periodic alterations in ventilation alone would promote oscillations in BP and HR. Seven healthy, wakeful subjects breathed in three patterns, as follows: (1) regular breathing (RB); (2) periodic breathing with three (PB3: cycle frequency = 0.035 Hz) augmented breaths alternating with 20-s apneas; and (3) periodic breathing with five (PB5: cycle frequency = 0.030 Hz) augmented breaths alternating with 20-s apneas. SaO2 remained above 95% throughout. During periodic breathing, peaks in BP and HR occurred during the ventilatory period and troughs occurred during apnea. The magnitudes of systolic BP oscillations increased significantly from RB (14 +/- 5 mm Hg) to PB3 (20 +/- 4 mm Hg) and PB5 (25 +/- 7 mm Hg; p < 0.005). HR oscillations also increased from regular breathing (13 +/- 6.0 beats/min) to PB3 (20.2 +/- 2.3 beats/min) and PB5 (20.2 +/- 4.7 beats/ min; p < 0.01). Spectral analysis showed that during periodic breathing there were discrete peaks in the spectral power of ventilation, BP, and R-wave-to-R-wave interval at the periodic breathing cycle frequencies. We conclude that oscillations in ventilation occurring during periodic breathing can amplify and entrain oscillations in BP and HR in the absence of hypoxia or arousals from sleep.

Adult↗

PubMed1999

Baroreflex control of heart rate in a canine model of obstructive sleep apnea.

We have recently demonstrated the development of systemic hypertension in a canine model of obstructive sleep apnea (OSA), but the underlying physiological mechanisms were not identified. Therefore, the purpose of this study was to examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in this canine model. OSA was produced in three dogs for 1 to 3 mo. Baroreflex control of HR was determined with graded infusions of vasoactive agents (phenylephrine and nitroprusside) administered over 30 to 60 s, during which steady-state systolic blood pressure (BP) and cardiac R-R interval responses were recorded. BP was measured with a permanently implanted arterial catheter and a telemetry system. Although, as previously reported, OSA resulted in increases in daytime (awake) mean BP of 6.0 to 26.8 mm Hg, there was no change in daytime baseline HR or in the slope of the systolic BP-R-R interval curve (p > 0.2). The findings demonstrate that OSA in the dog is associated with resetting of the baroreceptors to a higher pressure, but no change in baroreflex sensitivity.

Animals↗

PubMed1999

Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure.

In previous analyses of the occurrence of central (CSA) and obstructive sleep apnea (OSA) in patients with congestive heart failure (CHF), only men were studied and risk factors for these disorders were not well characterized. We therefore analyzed risk factors for CSA and OSA in 450 consecutive patients with CHF (382 male, 68 female) referred to our sleep laboratory. Risk factors for CSA were male gender (odds ratio [OR] 3.50; 95% confidence interval [CI], 1.39 to 8.84), atrial fibrillation (OR 4.13; 95% CI 1.53 to 11. 14), age > 60 yr (OR 2.37; 95% CI 1.35 to 4.15), and hypocapnia (PCO(2 )< 38 mm Hg during wakefulness) (OR 4.33; 95% CI 2.50 to 7. 52). Risk factors for OSA differed by gender: in men, only body mass index (BMI) was significantly associated with OSA (OR for a BMI > 35 kg/m(2), 6.10; 95% CI 2.86 to 13.00); whereas, in women, age was the only important risk factor (OR for age > 60 yr, 6.04; 95% CI 1.75 to 20.0). We conclude that historical information, supplemented by a few simple laboratory tests may enable physicians to risk stratify CHF patients for the presence of CSA or OSA, and the need for diagnostic polysomnography for such patients. Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure.

Atrial Fibrillation↗

PubMed1999

Dissociation between microneurographic and heart rate variability estimates of sympathetic tone in normal subjects and patients with heart failure.

The concept that spectral analysis of heart rate variability (HRV) can estimate cardiac sympathetic nerve traffic in subjects with both normal and impaired left ventricular systolic function has not been validated against muscle sympathetic nerve activity (MSNA). We used coarse-graining spectral analysis to quantify the harmonic and non-harmonic, or fractal, components of HRV and to determine low-frequency (0.0-0.15 Hz; PL) and high-frequency (0.15-0.5Hz; PH) harmonic power. To test the hypothesis that MSNA and HRV representations of sympathetic nerve activity (PL and PL/PH) increase in parallel in heart failure, we recorded heart rate and MSNA during supine rest in 35 patients (age 52.4+/-2 years; mean+/-S. E.M.), with a mean left ventricular ejection fraction of 22+/-2%, and in 34 age-matched normal subjects. Power density was log10 transformed. Mean MSNA was 52.9+/-2.6 bursts/min in heart failure patients and 34.9+/-1.9 bursts/min in normal subjects (P<0.0001). In normal subjects, but not in heart failure patients, total power (PT) (r=-0.41; P=0.02) and fractal power (PF) (r=-0.36; P=0.04) were inversely related to age. In heart failure patients, total and fractal power were reduced (P<0.009 for both), and were inversely related to MSNA burst frequency (r=-0.55, P=0.001 and r=-0.60, P=0. 0003 respectively). In normal subjects, there was no relationship between MSNA and either PL or PH. In heart failure patients, as anticipated, PH was inversely related to MSNA (r=-0.41; P<0.02). However, PL was also inversely rather than directly related to MSNA (r=0.44 for 1/log10 PL; P<0.01). There was no relationship between other sympathetic (PL/PH) or parasympathetic (PH/PT) indices and MSNA in either heart failure patients or normal subjects. The lack of concordance between these direct and indirect estimates of sympathetic nervous system activity indicates that this component of HRV cannot be used for between-subject comparisons of central sympathetic nervous outflow. It is the absence of low-frequency power that relates most closely to sympathetic activation in heart failure.

Adult↗

PubMed1999

Effect of adenosine on heart rate variability in humans.

By stimulating afferent nerve endings in skeletal muscle, heart, kidney and the carotid body, adenosine infusion evokes a receptor-specific sympatho-excitatory reflex in humans that overrides its direct negative chronotropic effect. We tested the hypothesis that adenosine increases heart rate by suppressing parasympathetic and augmenting sympathetic components of heart rate variability. High-frequency (PH; 0.15-0.50 Hz) and low-frequency (PL; 0.05-0.15 Hz) components of heart rate variability total power (PT) were determined by spectral analysis. The ratios PH/PT and PL/PH respectively were used to estimate parasympathetic and sympathetic input to the sino-atrial node. Heart rate was recorded before and during a 5 min intravenous infusion of adenosine (140 micrograms.min-1.kg-1) in seven healthy men. Adenosine did not affect blood pressure, but increased heart rate by 33+/-6 beats/min, and reduced PT, PH, PL and PH/PT. In contrast, there was an increase in PL/PH. In a second experiment in nine men, brachial artery infusion of adenosine (15 micrograms.min-1.100 ml-1 forearm tissue) increased heart rate by 3 beats/min, had no effect on PT, PH, PL or PH/PT, yet increased PL/PH. Intra-arterial adenosine exerts a modest effect on heart rate by modulating cardiac sympathetic indices, without affecting parasympathetic indices, of heart rate variability, whereas intravenous infusion of adenosine reduces heart rate variability and raises heart rate by decreasing parasympathetic and increasing cardiac sympathetic tone. These reflex effects may become clinically relevant during adenosine stress testing, or when endogenous adenosine is increased, such as during ischaemia, exercise or vasodepressor reactions, or in heart failure.

Adenosine↗

PubMed1999

Absence of heart rate increase during inferoposterior left ventricular hypoperfusion caused by dipyridamole infusion.

BACKGROUND: Stimuli such as inferoposterior myocardial infarction and right coronary injection with radiographic contrast media evoke a vasodepressor reflex characterized by bradycardia and hypotension (Bezold-Jarisch reflex). Dipyridamole acts by adenosine-mediated coronary vasodilation to disclose myocardial perfusion heterogeneity for thallium-201 scintigraphy. OBJECTIVE: To determine whether there is a relationship between the site of left ventricular hypoperfusion and the heart rate response to dipyridamole. DESIGN: One thousand eight hundred consecutive dipyridamole-thallium studies performed between 1985 and 1993 were reviewed to identify 48 subjects who met prespecified selection criteria. SETTING: Nuclear cardiology laboratory of a university teaching hospital. PATIENTS: Group 1 (n=26) had less than 5% pretest likelihood of coronary artery disease and normal thallium perfusion, group 2 (n=10) had isolated, completely reversible anterior perfusion abnormalities, and group 3 (n=12) had analogous inferoposterior perfusion abnormalities. INTERVENTIONS: Heart rate and blood pressure were recorded at baseline and each minute of supine dipyridamole infusion. MAIN RESULTS: After 4 mins of dipyridamole infusion, a significant increase in heart rate was observed in group 1 (+12 beats/min, P<0.05) and group 2 subjects (+12 beats/min, P<0.05) but not in group 3 subjects (+3 beats/min, not significant; P=0.016 compared with responses in the other two groups). Blood pressure was not affected by dipyridamole infusion in any group. CONCLUSIONS: Isolated, moderate or severe inferoposterior hypoperfusion in response to dipyridamole is not accompanied by an increase in heart rate, suggesting that the chronotropic response to dipyridamole is modulated by the presence and location of myocardial perfusion abnormalities. This observation is consistent with the concept that inhibition of adenosine reuptake by dipyridamole, leading to local increases of adenosine concentration, exerts direct and/or reflex effects on heart rate that are site specific. The absence of a rise in heart rate during dipyridamole infusion may be a marker of impaired coronary flow reserve in the inferoposterior left ventricular wall.

Coronary Disease↗

PubMed1999

1999 Canadian recommendations for the management of hypertension. Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension.

OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals on the management of hypertension in adults. OPTIONS: For patients with hypertension, there are both lifestyle options and pharmacological therapy options that may control blood pressure. For those patients who are using pharmacological therapy, a range of antihypertensive drugs is available. The choice of a specific antihypertensive drug is dependent upon the severity of the hypertension and the presence of other cardiovascular risk factors and concurrent diseases. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: MEDLINE searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (January 1993 to May 1998). Reference lists were scanned, experts were polled and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to levels of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS: Harms and costs: The diagnosis and treatment of hypertension with pharmacological therapy will reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and mortality. RECOMMENDATIONS: This document contains detailed recommendations pertaining to all aspects of the diagnosis and pharmacological therapy of hypertensive patients. With respect to diagnosis, the recommendations endorse the greater use of non-office-based measures of blood pressure control (i.e., using home blood pressure and automatic ambulatory blood pressure monitoring equipment) and greater emphasis on the identification of other cardiovascular risk factors, both in the assessment of prognosis in hypertension and in the choice of therapy. On the treatment side, lower targets for blood pressure control are advocated for some subgroups of hypertensive patients, in particular, those with diabetes and renal disease. Implicit in the recommendations for therapy is the principle that for the vast majority of hypertensive patients treated pharmacologically, practitioners should not follow a stepped-care approach. Instead, therapy should be individualized, based on consideration of concurrent diseases, both cardiovascular and noncardiovascular. VALIDATION: All recommendations were graded according to the strength of the evidence and the consensus of all relevant stakeholders. SPONSORS: The Canadian Hypertension Society and the Canadian Coalition for High Blood Pressure Prevention and Control.

Adult↗

PubMed1998

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure.

BACKGROUND: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep. METHODS AND RESULTS: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate. CONCLUSIONS: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.

Adult↗