Biomedical subjects

B R Walker

Publications and source records attributed to B R Walker.

At least 163 records · Page 9Linked to original sources

PubMed1989

Reduced erythrocyte deformability alters pulmonary hemodynamics.

Isolated rat lungs were perfused with suspensions containing normal and stiffened erythrocytes (RBCs) to assess the effect of altered RBC deformability on pulmonary hemodynamics. RBC suspensions were prepared using cells previously incubated in isosmolar phosphate-buffered saline with or without 0.0125 or 0.01875% glutaraldehyde. Washed RBCs were resuspended in isosmolar 4% albumin saline solution. Isolated rat lungs were perfused with control and stiffened cells by the use of a perfusion system that allowed rapid switching between suspensions. Pressure-flow (P/Q) curves were constructed by measuring pulmonary arterial pressure (Ppa) over a range of flow rates. In a second set of experiments, P/Q curves were generated for perfusion with control and stiffened cells (0.0125% glutaraldehyde) before and after vasoconstriction with a synthetic prostaglandin analogue (U 46619). RBC deformability was quantified in all experiments by determination of filtration time of a dilute cell suspension through a 4.7 microns Nuclepore filter. Incubation with 0.0125 or 0.01875% glutaraldehyde produced a 6 or 21% decrease in RBC deformability, respectively. These decreases in deformability were associated with significant increases in Ppa at each flow rate. The increases in Ppa correlated significantly with the degree of RBC stiffening. With 0.0125% glutaraldehyde, the P/Q curve was shifted upward without a change in slope, whereas incubation with 0.01875% glutaraldehyde resulted in a significant increase in slope. Vasoconstriction and perfusion with stiffened RBCs had additive effects on Ppa. These findings suggest that decreases in RBC deformability cause physiologically significant elevations in hemodynamic resistance in the pulmonary circuit independent of vasoactivity.

Animals↗

PubMed1988

Effect of chronic renal failure on oxaprozin multiple-dose pharmacokinetics.

The effects of renal disease on the steady-state kinetics of oxaprozin were assessed in eight patients on hemodialysis with normal serum albumin levels and eight normal subjects who received six doses. A larger clearance and volume of distribution at steady state for total and unbound oxaprozin occurred in the patients on hemodialysis. The elimination half-lives were not different. The mean total AUC, peak concentration, average steady-state plasma concentration, and trough concentration for total and unbound oxaprozin were decreased in the patients on hemodialysis. These differences are consistent with impaired absorption of oxaprozin in patients on hemodialysis. The higher dose-averaged unbound fraction of oxaprozin in plasma in patients on hemodialysis may be caused by endogenous binding inhibitors. Because clearance was not reduced in patients on hemodialysis, the dose of oxaprozin may not need to be reduced when albumin levels are normal.

Administration, Oral↗

PubMed1988

Hepatic safety of two analgesics used over the counter: ibuprofen and aspirin.

We evaluated the potential hepatic toxicity of ibuprofen, aspirin, and oxaprozin in 1468 patients with rheumatoid arthritis and osteoarthritis by slightly modifying an algorithm that was developed to evaluate the drug relatedness of renal toxicity associated with therapeutic doses of these agents in the same population. Ibuprofen proved to be the safest of these nonsteroidal antiinflammatory drugs; it was associated with no AST elevation that was considered probably drug related as determined by application of the algorithm to laboratory values and information from case report forms. The frequency of probably drug-related AST elevations was highest (5%) with aspirin; with oxaprozin, an investigational nonsteroidal antiinflammatory drug, the incidence (3%) fell between that for the other two agents. Thus our findings on the hepatic safety of ibuprofen are consistent with those in the medical literature.

Alanine Transaminase↗

PubMed1988

Cardiovascular responses to V1-vasopressinergic antagonism in conscious versus anesthetized rats.

Experiments were performed to compare the possible effect of endogenous arginine vasopressin on renal hemodynamics between anesthetized, surgically stressed rats and conscious rats. Animals were instrumented with arterial and venous catheters as well as with a pulsed Doppler flow probe on the left renal artery. The rats were studied under the following conditions: (1) conscious and unrestrained; (2) anesthetized only; (3) anesthetized with minor surgical stress; and (4) anesthetized with major surgical stress. Two anesthetic agents were also compared, a mixture of ketamine (110 mg/kg i.m.) and acepromazine (1 mg/kg i.m.), and sodium pentobarbital (50 mg/kg i.p.). Baseline mean arterial blood pressure was significantly higher in pentobarbital-anesthetized rats following surgical stress compared with conscious animals, but blood pressure was not affected by ketamine-acepromazine anesthesia. After baseline measurements of blood pressure, heart rate, and renal blood flow, a specific V1-vasopressinergic antagonist (d(CH2)5Tyr(Me) arginine vasopressin, 10 mg/kg i.v.) was administered to each group. Mean arterial blood pressure, heart rate, and renal blood flow were monitored for an additional 15 min. Mean arterial blood pressure and renal blood flow decreased after V1 antagonism in ketamine-acepromazine-anesthetized rats with major surgical stress, but were not affected in pentobarbital-anesthetized animals. Heart rate and renal vascular resistance were not affected following V1 blockade with either anesthetic agent. These data suggest that arginine vasopressin plays a role in maintaining blood pressure and renal perfusion in ketamine-acepromazine-anesthetized rats following surgical stress, but does not have a significant effect on renal hemodynamics under pentobarbital anesthesia.

Acepromazine↗

PubMed1988

Direct cardiac effects of vasopressin: role of V1- and V2-vasopressinergic receptors.

Experiments were performed to determine the possible direct effects of arginine vasopressin (AVP) on cardiac function in the nonworking Langendorff preparation. Hearts were isolated from male Wistar rats, and the coronary arteries were retrograde perfused at a constant rate through the aorta with a Krebs-Henseleit solution, which was continuously bubbled with 95% O2-5% CO2. The hearts were paced at 280 beats/min and measurements made of peak ventricular pressure (PVP), first derivative of left ventricular pressure (dP/dtmax), and coronary perfusion pressure (CPP). By maintaining constant coronary flow, the direct cardiac effects of AVP could be determined independent of changes in myocardial O2 delivery elicited by potential coronary vasoconstriction. Myocardial function was assessed at AVP concentrations of 0, 10, 25, 50, 100, 200, 400, and 500 pg/ml. Progressive coronary vasoconstriction was observed with increasing AVP concentration. In contrast, PVP and dP/dtmax increased at 50 and 100 pg/ml of AVP but fell at 400 and 500 pg/ml. The maximal PVP and dP/dtmax responses were at 50 pg/ml (+16 +/- 3 and +44 +/- 4%, respectively), whereas at 500 pg/ml both PVP and dP/dtmax were reduced below control (-30 +/- 4 and -34 +/- 5%, respectively). Pretreatment with the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (40 ng/ml) totally blocked both the coronary vasoconstrictor and contractility responses to AVP. Furthermore, infusion of a specific V2-agonist was without effect even at high doses. These data suggest that although AVP causes dose-related coronary vasoconstriction over a wide range of AVP concentrations, the hormone may exert a positive inotropic effect at doses mimicking circulating levels encountered in a number of pathophysiological situations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Renal vascular response to combined hypoxia and hypercapnia in conscious rats.

Experiments were performed to test for a possible role of arginine vasopressin (AVP) in the renal vascular responses to the combination of hypoxia and varying levels of CO2 in the conscious rat. Animals were instrumented with pulsed Doppler flow probes on the left renal artery and with arterial and venous catheters. Renal blood flow (RBF) and mean arterial blood pressure (MABP) were determined in conscious, unrestrained rats under the following conditions: 1) hypocapnic hypoxia [arterial PO2 (PaO2) = 26 Torr; arterial PCO2 (PaCO2) = 21 Torr]; 2) isocapnic hypoxia (PaO2 = 34 Torr; PaCO2 = 36 Torr); 3) hypercapnic hypoxia (PaO2 = 42 Torr; PaCO2 = 57 Torr); and 4) room air control (PaO2 = 93 Torr; PaCO2 = 38 Torr). MABP fell from 104 +/- 2 to 83 +/- 5 mmHg during hypocapnic hypoxia but was unaffected by the other stimuli. RBF was significantly reduced by both hypocapnic and hypercapnic hypoxia and unchanged in the other protocols, whereas renal vascular resistance (RVR) was elevated only in the hypercapnic hypoxia group. Additional experiments were performed to test whether activation of V1-vasopressinergic receptors during hypoxia might mediate the observed changes in renal hemodynamics. Experiments were performed as before except that at the midpoint of hypoxic or room air exposure, 10 micrograms/kg of the specific V1 vasopressinergic antagonist d(CH2)5Tyr(Me)AVP was administered. However, administration of the V1 antagonist had no effect on the observed renal hemodynamic responses to hypoxia. Therefore, although intense chemoreceptor stimulation by hypercapnic hypoxia may increase RVR and decrease renal perfusion, these renal hemodynamic responses do not appear to be mediated by increased circulating levels of AVP.

Animals↗

PubMed1988

Hemodynamic responses to vasopressinergic antagonism in water-deprived conscious rats.

Experiments were performed on conscious, chronically instrumented rats to determine the role of arginine vasopressin (AVP) on the systemic and regional hemodynamic effects of 48-h water deprivation. Arterial and venous catheters as well as pulsed Doppler flow probes were implanted in rats to measure cardiac output (CO), mesenteric blood flow (MBF), renal blood flow (RBF), or hindquarter blood flow (HQBF). After adequate recovery from surgey, euhydrated animals were administered a specific V1-vasopressinergic antagonist [d(CH2)5Tyr(Me)AVP, 10 micrograms/kg iv], a combined V1, V2-antagonist [d(CH2)5DTyr(Et)VAVP, 30 micrograms/kg iv], or saline vehicle (100 microliter/100 g). Neither antagonist was associated with any change in mean arterial blood pressure (MABP), heart rate (HR), systemic or regional flow or vascular resistance. All animals were subsequently water deprived for 48 h, at which time the experiments were repeated. Dehydration was associated with an increase in plasma AVP levels, hematocrit, and MABP but with a decrease in HR. Administration of either the combined V1, V2-antagonist or vehicle had no effect on any systemic or regional hemodynamic variables measured after 48-h dehydration. In contrast, although MABP, CO, MBF, and RBF were unaffected, V1-antagonism resulted in elevated HR, increased HQBF, and decreased hindquarter vascular resistance. In conclusion, AVP does not have a major effect on systemic hemodynamics in the dehydrated rat. However, certain beds may be affected by the relatively moderate levels of plasma AVP elicited during dehydration.

Animals↗

PubMed1988

Potentiated vasoconstrictor response to vasopressin following meclofenamate in conscious rats.

Experiments were performed to test the hypothesis that release of vasodilator cyclooxygenase products may attenuate the systemic and renal vasoconstrictor responses to arginine vasopressin (AVP) in the conscious, chronically instrumented rat. Four groups of animals were studied under the following conditions: (i) AVP infused iv at 2 ng/min for 40 min followed by a 15-min postcontrol; (ii) pretreatment with meclofenamate (3 mg/kg iv) followed by AVP infusion; (iii) meclofenamate pretreatment followed by saline vehicle infusion; and (iv) saline vehicle infusion alone (time control). AVP increased mean arterial blood pressure (MABP) in both meclofenamate-treated (n = 12) and untreated (n = 12) animals; however, the pressor response was significantly greater in animals with cyclooxygenase inhibition. Both heart rate (HR) and cardiac output (CO) (n = 6) fell during AVP infusion, but there were no differences between the meclofenamate-treated and the untreated groups. However, the total peripheral resistance response to AVP was significantly greater in animals treated with meclofenamate than the untreated group. Renal blood flow (RBF) was not affected by AVP infusion alone, but RBF fell significantly in animals given AVP after cyclooxygenase inhibition. The renal vascular resistance response to AVP was also enhanced by cyclooxygenase inhibition. There were no changes in any of the hemodynamic variables in either of the control protocols (i.e., meclofenamate alone or vehicle). These data demonstrate a consistent effect of cyclooxygenase inhibition to augment the systemic and renal vasoconstrictor responses to AVP, and suggest that endogenous vasodilator prostaglandins attenuate the potent vasoconstrictor action of this peptide in vivo.

Animals↗

PubMed1987

Cardiovascular effect of V1 vasopressinergic blockade during acute hypercapnia in conscious rats.

Experiments were performed to test the possible involvement of arginine vasopressin (AVP) in the systemic cardiovascular responses to acute hypercapnic acidosis in conscious chronically instrumented rats. Exposure to 6% CO2 caused arterial PCO2 to rise from 34 +/- 2 to 53 +/- 1 Torr. This level of hypercapnia was associated with a consistent bradycardia; however, cardiac output, blood pressure, and total peripheral resistance were not significantly affected. Administration of 10 micrograms/kg iv of the specific V1 vasopressinergic antagonist d(CH2)5Tyr(Me)AVP during 6% CO2 had no effect on any of the measured hemodynamic variables. Furthermore, d(CH2)5Tyr(Me)AVP also had no effect in normocapnic control animals. Exposure to a more severe level of hypercapnia (10% CO2, arterial PCO2 = 89 +/- 1 Torr) resulted in marked hemodynamic alterations. Profound bradycardia and decreased cardiac output in addition to increases in mean arterial blood pressure and total peripheral resistance were observed. V1 vasopressinergic antagonism during 10% CO2 had no effect on heart rate but greatly increased cardiac output. In addition, blood pressure fell and resistance was decreased below prehypercapnic levels. These data suggest that a number of the hemodynamic alterations associated with severe hypercapnic acidosis in the conscious rat may be mediated by the peripheral cardiovascular effects of enhanced AVP release.

Animals↗

PubMed1987

Effects of guanabenz on sodium and water homeostasis.

Sodium retention may partially offset the therapeutic action of some antihypertensive agents. To assess the effects of guanabenz on sodium balance, six men with mild to moderate hypertension were placed on diets with constant sodium intake (120 mEq/day) for approximately 4 weeks. After achieving sodium balance, the subjects received guanabenz (16-24 mg daily) for approximately 2 weeks. Mean supine blood pressure decreased from 144/93 to 133/86 mmHg during guanabenz treatment (p less than 0.001). Guanabenz therapy was associated with a decrease in body weight (mean +/- SE) from 85.4 +/- 7.0 to 84.4 +/- 6.8 kg (p less than 0.01). Sodium balance, glomerular filtration rate, plasma renin activity, mean maximal urine osmolality, fluid intake, urine volume, and serum sodium concentration were unchanged during guanabenz therapy. Three additional balance studies were performed during a period of greater sodium intake (180 mEq/day). Although higher doses of guanabenz were required to achieve blood pressure control, sodium balance still was not affected by the drug. Thus, an effective therapeutic dose of guanabenz administered for 2 weeks had no clinically significant effects on sodium or water homeostasis in patients with mild to moderate hypertension.

Adult↗

PubMed1986

Renal safety of two analgesics used over the counter: ibuprofen and aspirin.

The incidence of potentially serious drug-related elevations of BUN or serum creatinine was examined among 1468 patients with rheumatoid arthritis or osteoarthritis who took daily therapeutic doses of aspirin, ibuprofen, or oxaprozin, an investigational nonsteroidal antiinflammatory drug (NSAID), in multicenter clinical trials. Algorithms were developed to identify patients with potentially important elevations of these renal laboratory parameters and to assess the possible relation between these elevations and the study drugs. All three drugs were associated with a low (4% to 6%) incidence of potentially significant elevations in renal function parameters. Changes considered serious occurred in only three (less than 1%) patients (one treated with oxaprozin and two with ibuprofen), all of whom were receiving concomitant diuretic therapy. None of the changes led to adverse clinical consequences. Thus despite recent controversy regarding the renal safety of NSAIDs, all three drugs proved safe in these studies, despite the fact that aspirin and ibuprofen were given in doses equal to or higher than those used for over-the-counter indications.

Adult↗

PubMed1986

Effects of angiotensin II on plasma antidiuretic hormone and renal water excretion.

The effects of intravenous (i.v.) and intracarotid (IC) angiotensin II (AII) infusion on systemic and renal hemodynamics, renal water excretion, and plasma antidiuretic hormone (ADH) levels were examined in six conscious dogs under water loaded and hydropenic conditions. In the first group of seven studies, AII in a mean dose of 12.7 ng/kg/min was administered i.v. to water loaded dogs. The infusion induced a significant increase in mean arterial pressure (MAP, 99 to 118 mm Hg, P less than 0.001), and significant reductions in both glomerular filtration rate (GFR, 67 to 57 ml/min, P less than 0.05) and para-aminohippurate clearance (CPAH, 280 to 212 ml/min, P less than 0.005) occurred. Despite this decrement in renal hemodynamics, urine remained maximally dilute (Uosm, 58 to 61 mOsm/kg H2O, NS). Furthermore, plasma ADH was suppressed maximally after water load and did not increase after i.v. AII infusion. The IC infusion of AII (mean dose 5.8 ng/kg/min) produced similar changes in hemodynamics; plasma ADH remained undetectable. When AII was administered i.v. to hydropenic animals (mean dose 8.3 ng/kg/min), MAP again increased (86 to 111 mm Hg, P less than 0.001) as GFR (81.3 to 68.6 ml/min, NS) and CPAH (291 to 223 ml/min, P less than 0.05) declined modestly. In these animals, Uosm decreased significantly (1429 to 1114 mOsm/kg H2O, P less than 0.005) and plasma ADH did not change significantly (1.66 to 1.88 pg/ml, NS). When IC AII (4 ng/kg/min) was repeated in hydropenic dogs pretreated with indomethacin, neither Usom (1787 to 1664 mOsm/kg H2O, NS) nor plasma ADH were altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1986

The acute and chronic effects of indoramin on renal function, hemodynamics, and transport.

The acute and chronic renal effects of indoramin, an alpha 1-adrenoceptor antagonist, were investigated in six normotensive men (mean +/- SEM age, 36 +/- 3 years). Renal clearance studies were done during steady-state water diuresis before administration of indoramin (baseline), 3-4 h after a single 50-mg oral dose (acute study), and after 7 days of treatment with 25 mg twice daily (chronic study). After a single 50-mg oral dose, mean supine blood pressure decreased from 117/76 mm Hg at baseline to 109/74 mm Hg (NS), and glomerular filtration rate and renal blood flow were unchanged. There were small decreases (0.05 less than p less than 0.1) in the fractional excretion of sodium and potassium. After chronic administration (7 days) of indoramin, no significant changes in blood pressure, renal function, renal hemodynamics, or fluid and electrolyte excretion were observed. Mean body weight tended to decrease and fractional sodium excretion increased slightly (NS) after 7 days of indoramin. Plasma renin and aldosterone concentrations tended to increase (NS) after chronic indoramin administration. The results of this study indicate that acute and chronic administration of indoramin does not adversely affect renal function, renal hemodynamics, or fluid and electrolyte excretion in normotensive subjects.

Administration, Oral↗

PubMed1986

Evidence for a vasodilatory effect of vasopressin in the conscious rat.

Experiments were performed on conscious, chronically instrumented rats to determine the cardiovascular effects of intravenous arginine vasopressin (AVP) with and without V1-vasopressinergic antagonist administration. This design allowed the assessment of the cardiovascular effects of high circulating levels of AVP in the absence of the direct vasoconstrictor properties of the hormone. One group of rats (n = 10) were administered a constant infusion of AVP (2.5 mU/min iv) for 40 min and demonstrated increased mean arterial blood pressure (MABP) and total peripheral resistance (TPR), while heart rate (HR) and cardiac output (CO) fell. Another group of animals (n = 7) also received AVP for 40 min; however, at 25 min of the infusion, 10 micrograms/kg of d(CH2)5Tyr(Me)AVP was given intravenously. Administration of this V1-vasopressinergic antagonist caused MABP and TPR to fall below pre-infusion levels, although AVP infusion continued. HR and CO returned to control. Additional experiments showed no effect of the antagonist (n = 8) or AVP vehicle (n = 7) alone on the measured hemodynamic variables. In addition, pretreatment with the cyclooxygenase inhibitor meclofenamate did not affect the observed vasodilation in AVP-treated animals given the antagonist. A final group of animals (n = 6) was pretreated with d(CH2)5Tyr(Me)AVP prior to AVP infusion. On AVP administration, TPR fell in all animals. These data suggest that AVP exerts a vasodilatory effect unrelated to stimulation of V1-vasopressinergic receptors or arterial baroreceptors, which may partially offset the potent vasoconstrictor properties of this peptide.

Animals↗

PubMed1986

Role of vasopressin in the cardiovascular response to hypoxia in the conscious rat.

Previous experiments have demonstrated that hypoxia stimulates the release of arginine vasopressin in conscious animals including the rat. The present study was designed to test whether AVP may exert a vasoconstrictor influence during hypoxia at varying levels of CO2. Systemic hemodynamics were assessed in conscious rats for 30 min under hypocapnic hypoxic, isocapnic hypoxic, hypercapnic hypoxic, and room air conditions. Progressive effects on heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were observed with varying CO2 under hypoxic conditions. Hypocapnic hypoxia [arterial PO2 (PaO2) = 32 Torr; arterial PCO2 (PaCO2) = 22 Torr] caused HR and CO to rise and TPR to fall. Isocapnic hypoxia (PaO2 = 36 Torr; PaCO2 = 35 Torr) was associated with no significant changes in HR and CO or TPR, whereas hypercapnic hypoxia (PaO2 = 35 Torr; PaCO2 = 51 Torr) caused HR and CO to fall and TPR to rise. Room air time control experiments were associated with no change in measured hemodynamic variables. To determine the possible role of circulating AVP on these cardiovascular responses, additional experiments were performed where the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (10 micrograms/kg iv) was administered at the midpoint of hypoxic exposure. Antagonist administration had no effect on hypocapnic hypoxic animals or animals breathing room air; however, blood pressure and TPR were significantly reduced by d(CH2)5Tyr(Me)AVP in both isocapnic and hypercapnic hypoxic animals. The heart rate response to hypoxia at the various CO2 levels was unaffected; however, cardiac output and stroke volume were increased after V1-antagonism in the isocapnic and hypercapnic hypoxic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Reduced osmotic and nonosmotic release of vasopressin after meclofenamate in the conscious dog.

Both in vivo as well as in vitro experiments suggest that prostaglandins (PG) may influence arginine vasopressin (AVP) release. Recent studies on conscious dogs have shown that cyclooxygenase inhibition with meclofenamate reduces basal AVP release as well as AVP release in response to hypoxia. The current experiments were performed in order to test whether PG synthesis inhibition affects osmotic- and nonosmotic-stimulated AVP release in a similar manner. Osmotic AVP release was tested by slowly infusing hypertonic saline intravenously in water-diuresing dogs and serially sampling plasma for AVP concentration. Experiments were performed both with and without meclofenamate (2 mg/kg and 2 mg X kg-1 X h-1 iv) pretreatment. AVP release to a comparable osmotic stimulus was greatly reduced after meclofenamate administration. Nonosmotic AVP release was tested by inducing systemic hypotension with an intravenous infusion of nitroprusside. Hypotension was associated with an increase in AVP concentration, which was partially blunted after meclofenamate administration. Experiments performed with only a saline vehicle administered showed no decrease in AVP release in response to comparable hypotension. The findings of these studies suggest that endogenous PG may be involved in both osmotic and nonosmotic AVP release in the conscious dog.

Animals↗

PubMed1985

The uricosuric effect of oxaprozin in humans.

The effects of oxaprozin, a new investigational propionic acid analogue, and indomethacin on uric acid metabolism were compared in 12 healthy volunteers receiving either agent, first as a single dose and then daily for seven days. While indomethacin did not alter either serum or urinary uric acid values, oxaprozin caused a fall in serum uric acid levels from 5.8 +/- 0.2 mg/dL to 4.8 +/- 0.4 mg/dL (P less than 0.01). Urinary uric acid excretion rose from a baseline of 673 +/- 47 mg to 825 +/- 66 mg/24 h by day 7 of treatment (P less than 0.01). Since oxaprozin was associated with no change in glomerular filtration rate in these studies, the hypouricemic effect of oxaprozin is most likely a result of its direct uricosuric action. Because indomethacin and oxaprozin both are inhibitors of urinary prostaglandin E2 excretion, the data suggest that prostaglandin inhibition per se is not associated with changes in uric acid excretion.

Anti-Inflammatory Agents↗

PubMed1985

Reassessment of verbal and visual analog ratings in analgesic studies.

The relative performance of three analgesic rating scales--visual pain analog, verbal pain intensity, and verbal pain relief--was assessed in clinical trials with 1,497 patients and a variety of pain models. The scales correlated strongly with one another, with inconsistent and generally minimal differences in sensitivity. Overall, the verbal relief scale tended to be slightly more sensitive than the pain analog rating, which in turn showed a small advantage over the verbal pain intensity assessment. When the scores derived from the categorized ratings 1 hour after drug dosing (generally the time of peak effect) were analyzed, there was little difference whether a parametric or nonparametric approach was taken. When the cumulative measures of overall effect over 6 hours were considered, however, the nonparametric approach was decidedly more powerful. There was a similar pattern when the analog scores were analyzed. This unanticipated finding appears to be due to the cumulative measures (from all three scales) being more skewed toward the lower end of their respective ranges than are the 1-hour scores. A composite efficacy variable was defined, incorporating data from the three primary scales; this measure was found to be generally comparable in sensitivity to the individual scales and may be useful as a global summary of response. While our investigation provides evidence that any of the ratings considered will accurately reflect analgesic response, the verbal relief scale was the most sensitive and might be the best choice if a single measure is desired.

Bridged Bicyclo Compounds, Heterocyclic↗