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Biomedical subjects

M B Murphy

Publications and source records attributed to M B Murphy.

At least 19 recordsLinked to original sources
PubMed1995

Differential effects of chronic oral antihypertensive therapies on systemic arterial circulation and ventricular energetics in African-American patients.

BACKGROUND: A comprehensive evaluation of arterial load characteristics and left ventricular energetics in systemic hypertension has been limited by the need for invasive techniques to access instantaneous aortic pressure and flow. As a consequence of this methodological limitation, no data exist on the effects of long-term antihypertensive therapy on global arterial impedance properties and indexes of myocardial oxygen consumption (MVO2). Using recently validated noninvasive techniques, we compared in hypertensive patients the effects of chronic oral treatment with ramipril, nifedipine, and atenolol on arterial impedance and mechanical power dissipation as well as indexes of MVO2. METHODS AND RESULTS: Sixteen African-American subjects with systemic hypertension were studied with a randomized, double-blind, crossover protocol. Instantaneous central aortic pressure and flow, from which arterial load characteristics can be derived, were estimated from calibrated subclavian pulse tracings (SPTs) and continuous-wave aortic Doppler velocity in conjunction with two-dimensional (2D) echocardiographic measurements of the aortic annulus, respectively. To derive ventricular wall stress and indexes of MVO2, left ventricular short- (M-mode) and long-axis (2D echo) images were acquired simultaneously with SPTs. Data were collected at the end of a 2-week washout period (predrug control) and after 6 weeks of treatment with each agent. Although all three agents reduced diastolic blood pressure to the same extent, different effects on mean and systolic pressures and vascular impedance properties were noted. Nifedipine reduced total peripheral resistance (TPR; 1744 +/- 398 versus 1290 +/- 215 dyne-s/cm5) and increased arterial compliance (ACL; 1.234 +/- 0.253 versus 1.776 +/- 0.415 mL/mm Hg). This improvement in arterial compliance was not entirely accounted for by the reduction in distending pressure. Ramipril also decreased TPR (1740 +/- 292 versus 1437 +/- 290 dyne-s/cm5) and increased ACL (1.214 +/- 0.190 versus 1.569 +/- 0.424 mL/mm Hg), but with this agent, the change in arterial compliance was explained solely on the basis of a reduction in distending pressure. Atenolol, in contrast, did not affect either TPR or ACL. In agreement with the compliance results, nifedipine and ramipril significantly lowered the first two harmonics of the impedance spectrum, but atenolol did not. None of these agents resulted in a significant change in characteristic impedance or in the relative amplitude of the reflected pressure wave. Total vascular mechanical power and percent of oscillatory power remained unaltered with all antihypertensive treatments. Only ramipril and nifedipine reduced the integral of both meridional and circumferential systolic wall stresses, indicating that MVO2 per beat was reduced with these agents. Stress-time index, a measure of MVO2 per unit time, decreased significantly with ramipril but not with nifedipine because of an increase in heart rate noted in 10 of 16 patients (mean increase, 10 beats per minute). Thus, a reduction in MVO2 coupled with unchanged total vascular mechanical power suggests improved efficiency of ventriculoarterial coupling with ramipril and with nifedipine in the subset of patients in whom heart rate remained unchanged. In contrast, there was no evidence of a reduction in wall stress, stress integral, or stress-time index with atenolol. CONCLUSIONS: The noninvasive methodology used in this study constitutes a new tool for serial and simultaneous evaluation of arterial hemodynamics and left ventricular energetics in systemic hypertension. In this study, we demonstrate the differential effects of chronic antihypertensive therapies on systemic arterial circulation and indexes of MVO2 in African-American subjects. Consideration of drug-induced differential responses of arterial load and indexes of MVO2 with each drug may provide a more physiological approach to the treatment of systemic hypertension in indivi

Administration, Oral↗
PubMed1995

Prostacyclin and thromboxane levels in pleural space fluid during cardiopulmonary bypass.

Prostaglandins exhibit a variety of cardiovascular actions that may affect the hemodynamic recovery of the ischemic myocardium after cardiopulmonary bypass. We have observed a decrease in the mean arterial pressure on autotransfusion of the accumulated pleural cavity fluid during operation. One aim of this study was to determine the concentrations of prostacyclin and thromboxane A2 in the pleural cavity fluid by measuring their stable metabolites, 6-keto-PGF1 alpha and thromboxane B2, respectively, in 8 consecutive patients undergoing myocardial revascularization, and to compare them with the arterial levels. A second aim was to quantify the hemodynamic effect of the pleural cavity fluid during operation. The concentration of 6-keto-PGF1 alpha in the pleural cavity fluid was significantly higher than the arterial concentration (mean, 21.6 +/- 18.2 ng/mL; p < 0.01). The concentration of thromboxane B2 was also raised compared with the arterial concentration (mean, 3.62 +/- 5.96 ng/mL; p < 0.2). The percentage fall in the mean arterial pressure was 29.7% +/- 8.86% (p < 0.02), which was transient and lasted 1 to 3.5 minutes. The hemoglobin concentration, potassium level, and pH were also measured. This study shows that the pleural cavity fluid during cardiac operations contains significant amounts of endogenous prostacyclin. Considering the potential benefit of prostacyclin on the recovering myocardium, we believe that this fluid should be transfused as a volume replacement, keeping in mind the transient phase of hemodynamic instability.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

The dual-specificity CLK kinase induces neuronal differentiation of PC12 cells.

CLK is a dual-specificity protein kinase capable of phosphorylating serine, threonine, and tyrosine residues. We have investigated the action of CLK by establishing stable PC12 cell lines capable of inducibly expressing CLK. Expression of CLK in stably transfected PC12 cells mimicked a number of nerve growth factor (NGF)-dependent events, including the morphological differentiation of these cells and the elaboration of neurites. Moreover, CLK expression enhanced the rate of NGF-mediated neurite outgrowth of these cells, indicating that CLK expression and NGF treatment activate similar signal transduction pathways. CLK expression, unlike NGF, was not able to promote PC12 cell survival in serum-free media, demonstrating that CLK only partially recapitulated the actions of NGF on these cells and that the biochemical pathways necessary for morphological differentiation can be stimulated without also stimulating those necessary for survival. Induction of CLK expression also resulted in the selective activation of protein kinases that are components of growth factor-stimulated signal transduction cascades, including ERK1, ERK2, pp90RSK, and S6PKII. Induction of CLK expression, however, did not stimulate pp70S6K or Fos kinase, two NGF-sensitive protein kinases. These data indicate that CLK action mediates the morphological differentiation of these cells through its capacity to independently stimulate signal transduction pathways normally employed by NGF.

Animals↗
PubMed1994

The use of ambulatory blood pressure monitoring in the evaluation of racial differences in blood pressure.

Ethnic differences in 24h blood pressure profiles exist, and 24h ambulatory blood pressure monitoring shows that blacks have a higher nocturnal blood pressure associated with a small diurnal change in pressure. Studies in adolescents suggest that these diurnal differences antedate adulthood. Nocturnal blood pressure may be independently important in the pathogenesis of left ventricular hypertrophy.

Adolescent↗
PubMed1992

Selecting optimum antihypertensive therapy: indications for choosing a calcium channel blocker.

In choosing the optimum antihypertensive agent for an individual patient, various factors should be considered. Demographic characteristics (e.g., age, gender, race) and the circadian pattern of blood pressure elevation may influence the response to therapy. Concomitant therapy for coexisting medical disorders must be evaluated for possible drug interactions. Calcium channel blockers, which can be used in any age group, may be particularly useful in hypertensive patients with certain concurrent conditions (e.g., coronary artery disease, migraine, or gastrointestinal motility disorders). Life-style, including occupation and leisure-time activities, may contraindicate the use of certain drugs in a particular patient. It also may be necessary to consider the economic status of the patient, particularly in the elderly, who often have limited disposable income. Since to a great extent successful therapeutic management of hypertension depends on patient compliance, reduced frequency of dosing (i.e., once or twice daily) is desirable. The clustering of morbid events in the hours immediately following awakening highlights the need for therapy that provides 24-hour control, thereby ensuring adequate pharmacodynamic effects during that crucial period. The challenge is to select the most appropriate first-line agent (diuretic, beta blocker, calcium channel blocker, or angiotensin-converting enzyme inhibitor) for a particular patient.

Age Factors↗
PubMed1992

Diurnal blood pressure variation and cardiac mass in American blacks and whites and South African blacks.

American blacks exhibit higher nocturnal blood pressure than American whites with similar daytime pressure. To determine whether this represents a true racial difference, as opposed to a consequence of different environmental factors, we measured ambulatory blood pressure, cardiac left ventricular mass, and urinary electrolyte excretion in 22 South African blacks (15 women, aged 36 +/- 12 years) and age, sex, and daytime mean pressure-matched American blacks and whites. While all three groups exhibited similar daytime blood pressure, American blacks displayed significantly higher nighttime mean blood pressure. Both African blacks and American whites experienced the same fall in nighttime blood pressure. Left ventricular mass index was highest in American blacks and lowest in South African blacks. Urine sodium excretion was similar in all groups, but both black populations excreted significantly less potassium than American whites. The data suggest that the differences in diurnal blood pressure rhythm between American blacks and whites do not represent a true racial difference, but more likely are environmental in origin. Furthermore, since both black populations had similar cation excretion rates, yet differed in blood pressure pattern and cardiac mass, divergence in dietary sodium or potassium intake cannot explain the ethnic group differences in the United States.

Adult↗
PubMed1992

5-Hydroxytryptamine receptor activity of the dopamine receptor agonist fenoldopam in canine tracheal smooth muscle.

Fenoldopam is a new vasodilator undergoing clinical trials for the treatment of hypertensive emergencies. Its pharmacologic effects result from activation of vascular dopamine-1 receptors. In canine tracheal smooth muscle strips, fenoldopam caused a concentration- and calcium-dependent increase in tension, which was not antagonized by atropine, indomethacin or the dopamine-1 receptor antagonist, SCH 23390. The EC50 (1.89 x 10(-6) M) exceeded that of serotonin or acetylcholine (8.38 x 10(-8) and 8.25 x 10(-8) M, respectively). Maximum tension was similar for fenoldopam and serotonin (11.6 +/- 1.5 g, n = 7 and 13.8 +/- 0.8 g, n = 24; P greater than .2) and considerably greater for acetylcholine (20.5 +/- 1.3 g, n = 14; P less than .005). The serotonin antagonists ketanserin and methysergide reversed completely the effect of fenoldopam (5 x 10(-7) M) with IC50 values of 2.5 x 10(-9) and 2.7 x 10(-9) M, respectively. Phentolamine, rauwolscine and chlorpheniramine were also effective, but they were less potent (IC50 values 6.6 x 10(-8), 1.0 x 10(-7) and 1.7 x 10(-7) M, respectively). By contrast, only very high concentrations (IC50, 5.3 x 10(-5) M) of terazosin produced an inhibition of fenoldopam-induced tension increases. The effect of antagonists could be overcome by increasing the fenoldopam concentration. Experiments performed on strips precontracted with serotonin (5 x 10(-8) M) revealed a very similar order of potency for the five antagonists. The addition of serotonin did not increase the tension produced by supramaximal concentrations of fenoldopam (and vice-versa), whereas acetylcholine increased tension further.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Electrocardiographic changes during acute treatment of hypertensive emergencies with sodium nitroprusside or fenoldopam.

BACKGROUND: Electrocardiograms are routinely obtained before and during the acute treatment of hypertensive emergencies, usually to rule out "ischemic changes." Despite a few anecdotal reports of electrocardiographic changes, little is known about the incidence and significance of such changes, or their relationship to the treatment used. METHODS: We prospectively analyzed 12-lead electrocardiograms from 21 patients admitted for hypertensive emergencies (average blood pressure, 222 +/- 4/140 +/- 3 mm Hg). Patients were randomly assigned to treatment with sodium nitroprusside (n = 11) or the dopamine receptor agonist fenoldopam mesylate (n = 10). Electrocardiograms were obtained at baseline and within 30 minutes of reaching goal blood pressure (diastolic blood pressure, 100 to 110 mm Hg). RESULTS: There was no significant effect of either drug treatment on PR interval, QRS duration, QT interval, or R-wave amplitude, and no major ST-segment changes were noted. During treatment with either drug, the average T-wave amplitude decreased in all leads except aVR. New T-wave inversions in lead V4 occurred in two and four patients after fenoldopam and nitroprusside treatment, respectively. There were no clinically apparent episodes of myocardial ischemia in any patient. CONCLUSIONS: Even in the absence of obvious myocardial ischemia, a decrease in T-wave amplitude, including T-wave inversion, occurs commonly during acute blood pressure reduction in hypertensive emergencies, an observation that may be explained by the accompanying acute changes in cardiac chamber volumes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Blood pressure and fitness for work.

A survey was carried out to determine whether physicians in Occupational Medicine exclude job applicants because of hypertension and to examine the critical blood pressure cut-off values they apply. The survey sampled 116 respondents, members of the American Occupational Medical Association, Central States. Of these, 33 (28%) reported excluding hypertensives from work permanently, as the policy of one or more of the companies they serve. Another 78 physicians (68%) reported excluding hypertensives permanently on their own initiative when there was no company policy. The critical determining diastolic pressure varied from 90 to greater than 130 mm Hg; 22 respondents (19%) excluded individuals with mild hypertension. The results demonstrate that blood pressure is frequently used as a criterion for employment. Additionally, the level of blood pressure precluding work is arbitrary and variable. There is a need for consensus on appropriate guidelines to preclude inappropriate discrimination against hypertensive job applicants.

Blood Pressure↗
PubMed1991

Influence of diuretic therapy on the clonidine suppression test.

Moduretic has been reported to inhibit the suppression of plasma norepinephrine (NE) levels by the alpha 2 adrenoceptor agonist, clonidine. To determine whether plasma volume reduction by hydrochlorothiazide (HCTZ) or antagonism of Na+/H+ exchange by amiloride (the constituents of Moduretic) is responsible, the authors performed a modified clonidine suppression test (CST) in nine normal volunteers (aged 25 +/- 2 years), pretreated for 1 week with HCTZ 50 mg daily, amiloride 10 mg daily, or placebo, in a randomized, double-blind, crossover study. Baseline characteristics were identical on all study days, except serum [K+] and weight, which were lowest on HCTZ (3.6 +/- 0.2 mEq/L and 78.7 +/- 2.5 kg), compared with amiloride (4.2 +/- 0.1 mEq/L and 79.9 +/- 2.4 kg) and placebo (4.0 +/- 0.1 mEq/L and 80.2 +/- 2.7 kg, P less than .05). Oral clonidine (0.3 mg) produced a reduction in mean blood pressure by about 20%. Plasma norepinephrine levels were similar in patients receiving placebo, HCTZ, and amiloride (205 +/- 18, 272 +/- 40 and 277 +/- 44 pg/mL, P greater than .20), and decreased significantly during CST. The maximal reduction for each subject averaged 72.7 +/- 12.4%, 87.9 +/- 3.8%, and 82.9 +/- 5.7% for placebo, HCTZ, and amiloride. Clonidine also produced a four to seven-fold increase in plasma growth hormone levels, reduced salivary flow by about 75%, and increased the level of sedation. There were no differences among the three pretreatment regimens in the effects of clonidine, indicating that diuretic therapy does not need to be systematically discontinued in patients undergoing CST.

Adult↗
PubMed1991

A double-blind, randomized, placebo-controlled comparison of the metabolic effects of low-dose hydrochlorothiazide and indapamide.

To compare the metabolic effects of indapamide (I) and hydrochlorothiazide (HCTZ) at equivalent hypotensive doses, 11 hypertensive patients (5 male, 8 black, aged 56 +/- 8 yr--mean +/- SEM) having serum uric acid concentrations greater than 8.0 mg/dL while receiving previous therapy with thiazides, received 28-day courses of placebo, indapamide (2.5 mg/d), and HCTZ (25 mg/d) in randomized, double-blind, double-crossover design. Supine and standing blood pressures, weight, pulse rates and sera were obtained after each 28 day period. Blood pressures and weights were lowered (P less than .001 and 0.01, respectively) equally by the diuretics: supine blood pressures fell from 168 +/- 4/104 +/- 2 (placebo) to 153 +/- 4/93 +/- 2 (HCTZ) and 155 +/- 4/94 +/- 2 mm Hg (I); standing blood pressures (after 2 minutes upright) also decreased: 171 +/- 5/104 +/- 2 (placebo) to 156 +/- 5/93 +/- 2 (HCTZ) and 157 +/- 4/94 +/- 2 mm Hg (I). There was a statistically significant difference (P less than .05) across treatments by analysis of variance in both uric acid and potassium concentrations: serum urate (in mg/dL) was lowest with placebo (7.1 +/- 0.3), and rose to 8.3 +/- 0.2 with HCTZ (P less than .001 compared with placebo by paired t test), and 8.1 +/- 0.2 with I (P less than .005 vs. placebo). The urate concentration with I was significantly lower than that with HCTZ (P less than .02), but the magnitude of the difference was small (0.2 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Intraocular pressure increases with fenoldopam, but not nitroprusside, in hypertensive humans.

Fenoldopam mesylate stimulates adenyl cyclase in porcine ocular trabecular meshwork and raises intraocular pressure in humans. To clarify whether this results from direct activation of the dopamine-1 receptor or indirectly from baroreflex sympathetic stimulation after blood pressure reduction, intraocular pressure was measured in 14 patients with accelerated/malignant hypertension, randomized between intravenous fenoldopam or sodium nitroprusside. Intraocular pressure was measured with a Perkins tonometer, before and at the twentieth minute of each dose increment. In seven patients with a mean blood pressure of 232/131 mm Hg treated with fenoldopam, intraocular pressure increased in a dose-dependent fashion, from 16 +/- 1 to 20 +/- 2 mm Hg (p less than 0.005). In contrast, seven patients with a mean blood pressure of 225/134 mm Hg treated with sodium nitroprusside exhibited no change in intraocular pressure (15 +/- 1 versus 14 +/- 1 mm Hg) despite similar blood pressure reduction. Increases in heart rate were not significantly different. Rates of urinary excretion of norepinephrine plus epinephrine increased significantly relative to baseline (p less than 0.05) but were not different between groups. These data suggest that the increase in intraocular pressure with fenoldopam results from specific activation of the dopamine-1 receptor and is not caused by baroreflex sympathetic stimulation. Because dopamine-1 receptors may modulate intraocular pressure, dopamine-1 receptor blockers might be useful therapy for glaucoma.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Selective role of dopamine in the natriuresis produced by iso-osmotic saline infusion.

Endogenous dopamine (DA) selectively contributes to the natriuresis (UNaV) produced by infusion and dietary consumption of sodium chloride. The present study in anesthetized rats determined whether DA has a role in the natriuresis produced by small (2.0 +/- 0.11% increase in body weight) and large (17.9 +/- 0.58% increase in body weight) increments in extracellular fluid volume with iso-osmotic saline. Small volume expansion increased urine flow (V) by 59 +/- 15%, UNaV by 155 +/- 31%, and dopamine excretion by 25 +/- 9%. DA1-receptor blockade with SCH 23390 (SCH, 1.0 microgram/kg/min), attenuated the natriuresis; an increase in UNaV of only 69 +/- 15%. Large volume expansion increased V by 1,026 +/- 215% and UNaV by 2,735 +/- 899%, without affecting dopamine excretion. Increments in V and UNaV were unaffected by increasing doses of SCH (1.0 microgram/kg/min; 10 micrograms/kg/min; and 50 micrograms/kg bolus, followed by 10 micrograms/kg/min). Adequacy of DA1-receptor blockade was demonstrated by the fact that SCH (1.0 microgram/kg/min) attenuated the natriuresis produced by the DA1-receptor agonist, fenoldopam (0.1 micrograms/kg/min ia). We conclude that endogenous DA contributes to the natriuresis produced by small, but not large, increases in extracellular fluid volume with iso-osmotic saline.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Diurnal blood pressure variation: differences among disparate ethnic groups.

We examined the possibility that excess cardiovascular morbidity in American blacks compared with whites might be partly the result of differences in diurnal blood pressure variation. Urban American blacks have higher night-time blood pressures and show a smaller increase in blood pressure during the waking day than whites. This difference is associated with a higher cardiac mass in the blacks and occurs despite similar duration and quality of sleep in blacks and whites. Both groups show similar levels of sympatho-adrenal activity at night, but the diurnal increase is smaller in blacks, paralleling the smaller increase in blood pressure. In Africa blacks show a diurnal pressure pattern similar to American whites. Disparities in cation consumption do not explain the differences in blood pressure variation between these groups.

Black People↗
PubMed1990

Williams syndrome in twins.

Two sets of identical twins with Williams syndrome have been reported previously. We report on 2 additional sets of presumed identical twins with Williams syndrome. All 4 patients had the typical Williams syndrome facial appearance, growth deficiency, and developmental delay. None of the patients had supravalvular aortic stenoses; however, all were diagnosed as having probable distal pulmonary artery stenosis. In the set of twins in which serum calcium was measured, one twin had an elevated serum ionized calcium level. These 2 sets of twins further document the occurrence of Williams syndrome in identical twins. To our knowledge, there are no reported cases of concordance in dizygotic twins. This adds further support to the likelihood that Williams syndrome is a genetic disorder.

Abnormalities, Multiple↗