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Biomedical subjects

R L Royster

Publications and source records attributed to R L Royster.

At least 19 recordsLinked to original sources
PubMed2000

Prophylactic nitroglycerin did not reduce myocardial ischemia during accelerated recovery management of coronary artery bypass graft surgery patients.

OBJECTIVE: To evaluate the use of a high dose of nitroglycerin (NTG) for prophylaxis against myocardial ischemia and infarction in patients undergoing coronary artery bypass graft (CABG) surgery with accelerated recovery. DESIGN: Prospective, double-blind, placebo-controlled randomized study. SETTING: A university-based medical center. PARTICIPANTS: Forty adult patients presenting for elective CABG surgery. INTERVENTIONS: Forty patients were divided into 2 blinded study groups. Twenty patients received 2 microg/kg/min of NTG starting before induction of anesthesia and continuing for 6 hours after extubation in the intensive care unit. The placebo group (n = 20) received normal saline during this same interval. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, incidence and severity of myocardial ischemia, and myocardial infarction rates were determined. There were no differences in hemodynamic parameters between groups. The incidence of ischemia was approximately 35% in each group. Myocardial infarction (as determined by elevated creatine kinase-MB fraction, troponin I, and electrocardiogram criteria) was 10% in the placebo group and 5% in the NTG group (p = 0.234). CONCLUSIONS: This study shows a high incidence of myocardial ischemia and infarction in patients presenting for CABG surgery with an accelerated recovery management scheme. NTG was well tolerated clinically; however, it was not found to be protective against myocardial ischemia or infarction in this setting.

Adult↗
PubMed1999

The safety and effectiveness of esmolol in the perioperative period in patients undergoing abdominal aortic surgery.

OBJECTIVES: To determine (1) if perioperative use of esmolol in major vascular surgery patients provides strict heart rate (HR) control, (2) what doses of esmolol are required to do this, and (3) does this control influence myocardial ischemia or result in adverse consequences. DESIGN: Prospective study of 40 patients randomized to two groups: The HR was controlled to either less than 80 beats/min (group 80) or less than 110 beats/min (group 110) using esmolol. Patients were monitored continuously for electrocardiographic changes perioperatively. HR control began after induction of anesthesia and continued for 48 hours thereafter. SETTING: Operating room and intensive care unit. PATIENTS: Patients undergoing abdominal vascular surgery involving aortic cross-clamping. INTERVENTIONS: Esmolol was titrated until the target HR was met. MEASUREMENTS AND RESULTS: Only one patient demonstrated an adverse effect. The median infusion rates were 100 and 12.5 microg/kg/min for groups 80 and 110. Target HR was met less in group 80 than in group 110, primarily in the postoperative period. Ischemia patterns were not significantly different between groups. CONCLUSION: Using esmolol for HR control in the intraoperative period for abdominal vascular surgery patients is effective and safe. HR control was much less effective in the postoperative period, but esmolol is safe when used at recommended doses. Further study with a larger number of patients is necessary to determine whether strict HR control with esmolol affects the incidence of myocardial ischemia or infarction in this patient population.

Adrenergic beta-Antagonists↗
PubMed1999

A randomized, blinded trial of the antioxidant pegorgotein: no reduction in neuropsychological deficits, inotropic drug support, or myocardial ischemia after coronary artery bypass surgery.

OBJECTIVE: To determine whether patients receiving pegorgotein preoperatively would be less likely than patients receiving placebo to demonstrate postoperative cerebral or myocardial dysfunction and thus would be less likely to (1) demonstrate a decline in neuropsychologic testing after cardiopulmonary bypass, (2) receive inotropic drug support, or (3) demonstrate electrocardiographic signs of ischemia or infarction. DESIGN: Prospective, randomized, blinded clinical trial. SETTING: University teaching hospital and clinics. PARTICIPANTS: Sixty-seven patients with normal left ventricular function undergoing elective, primary coronary artery bypass surgery. INTERVENTIONS: Six to 18 hours before aortic cross-clamping, patients received a single dose of placebo (n = 22); pegorgotein, 2,000 IU/kg intravenously (n = 23); or pegorgotein, 5,000 IU/kg intravenously (n = 22). MEASUREMENTS AND MAIN RESULTS: Patients in the three groups were similar; the mean ages were 65, 66, and 67 years, and there were seven, eight, and seven women in the placebo; pegorgotein, 2,000 IU/kg; and pegorgotein, 5,000 IU/kg groups. Fifty-one of 67 patients demonstrated neuropsychologic deficit 5 to 7 days postoperatively (n = 17, 19, and 15 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = NS). Median duration of cardiopulmonary bypass was longer in patients with two or more deficits at 4 to 6 weeks than in those with fewer than two deficits (121 v. 98 minutes; p = 0.04). No patient demonstrated a perioperative stroke. Twenty-seven patients required inotropic drug support after cardiopulmonary bypass (n = 8, 11, and 8 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = NS). Inotropic drug support was associated with history of angina (p = 0.01) and increasing weight (p = 0.03). Nine patients demonstrated early postoperative ischemia or infarction (n = 1, 7, and 1 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = 0.07). CONCLUSIONS: This study showed no positive influence of pegorgotein on the incidence of any of the findings and showed a trend toward an increased incidence of myocardial ischemia or infarction.

Aged↗
PubMed1998

Factors that predict the use of positive inotropic drug support after cardiac valve surgery.

UNLABELLED: Left ventricular dysfunction is common after cardiac surgery and is often treated with positive inotropic drugs (PIDs). We hypothesized that the use of PIDs after cardiac valve surgery would have significant associations with the valvular pathophysiology and surgical procedure, and unlike the case for patients undergoing coronary artery surgery, would be unrelated to duration of cardiopulmonary bypass (CPB) or of aortic clamping. One hundred forty-nine consenting patients undergoing cardiac valve surgery were studied. Patients with hepatic or renal failure, or New York Heart Association class IV cardiac symptoms, were excluded. Patients were considered to have received PIDs if they received an infusion of amrinone, dobutamine, epinephrine, or dopamine (> or = 5 microg x kg[-1] x min[-1]). PIDs were received by 78 patients (52%). In a univariate model, older age, history of congestive heart failure, decreasing left ventricular ejection fraction, longer durations of CPB, and concurrent coronary artery surgery significantly increased the likelihood of PID support. There was also significant variation by anesthesiologist in the administration of PIDs. The specific diseased valve and valvular stenosis or insufficiency did not influence the likelihood of receiving PID support. In a multivariable model, age, history of congestive heart failure, decreasing left ventricular ejection fraction, and anesthesiologist were significantly associated with the likelihood of PID support, but duration of CPB and concurrent coronary artery surgery were not. In conclusion, patient age and ventricular function, as well as physician preferences, predicted the need for inotropic drug support; however, neither the specific valvular lesion, nor duration of CPB were strongly predictive in a multivariable model. IMPLICATIONS: We evaluated factors related to use of positive inotropic drugs after cardiac valve surgery. The likelihood of a patient receiving these drugs increases with advancing age and with more severe preoperative left ventricular dysfunction, but was not influenced by the specific diseased valve or the duration of cardiopulmonary bypass.

Amrinone↗
PubMed1998

A multicenter, randomized, blind comparison of amrinone with milrinone after elective cardiac surgery.

UNLABELLED: Amrinone and milrinone are phosphodiesterase inhibitors with positive inotropic effects useful for the treatment of ventricular dysfunction after cardiac surgery. Forty-four patients undergoing elective cardiac surgery at four centers received either amrinone (n = 22) or milrinone (n = 22) in a randomized, blind fashion. Immediately after separation from cardiopulmonary bypass (CPB), two bolus doses of either amrinone 0.75 mg/kg or milrinone 25 microg/kg were administered over 30 s, separated by 5 min. Hemodynamic measurements were recorded before each dose and at the end of the 10-min study. Both amrinone and milrinone increased the cardiac index (48% vs 52%, P = not significant [NS] for amrinone and milrinone, respectively). There was a small increase in mean arterial pressure (MAP) after amrinone administration (from 68 +/- 3 to 72 +/- 3 mm Hg at 10 min, P < 0.05) with no significant change in MAP after milrinone administration. Central venous pressure was significantly higher in the amrinone group at baseline and 5 min (12 vs 10 mm Hg and 11 vs 10 mm Hg, respectively; P < 0.05). Systemic and pulmonary vascular resistances decreased significantly and to a similar extent after either amrinone or milrinone administration. Phenylephrine was required in 11 of 22 patients receiving amrinone and in 11 of 22 patients receiving milrinone to maintain arterial blood pressure. The proportion of patients requiring an intravascular volume infusion (15 of 22 vs 17 of 22, P = NS) and the total fluid volume infused were similar (402 +/- 57 vs 350 +/- 49 mL, P = NS for amrinone and milrinone, respectively). Amrinone and milrinone seem to have similar hemodynamic effects after CPB, with the exception of blood pressure, although the need for vasopressor support of blood pressure did not differ. Selection between these two drugs may include nonhemodynamic considerations such as cost. IMPLICATIONS: Amrinone and milrinone are drugs that improve cardiac contraction. Their effects have never been directly compared in patients. We found that amrinone and milrinone produced similar hemodynamic effects in adult patients undergoing cardiac surgery. Choice between the two drugs can be based on nonhemodynamic considerations such as cost.

Adult↗
PubMed1998

Dobutamine antagonizes epinephrine's biochemical and cardiotonic effects: results of an in vitro model using human lymphocytes and a clinical study in patients recovering from cardiac surgery.

BACKGROUND: Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects. METHODS: The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10(-8) to 10(-4) M) or epinephrine (10(-9) M to 10(-5) M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 microg x kg(-1) x min(-1)) or epinephrine (10, 20, or 40 ng x kg(-l) x min(-1)), alone or in combination. RESULTS: In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration approximately 200%. However, when epinephrine (10(-6) M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10(-6) to 10(-4) M (P = 0.001). In patients, 1.25 to 5 microg x kg(-1) x min(-1) dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5microg x kg(-1) x mi(-1)) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 microg x kg(-1) x min(-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects. CONCLUSIONS: Dobutamine inhibits epinephrine-induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.

Adrenergic Agonists↗
PubMed1997

Cloricromene reduces myocardial infarct size in rabbits when administered during the early reperfusion period.

Cloricromene is a coumarin derivative without anticoagulant activities that has recently been found to decrease myocardial infarct size after an ischemic-reperfusion injury. This study seeks to determine when the cardioprotective action of cloricromene is exerted in an in vivo rabbit model of ischemic-reperfusion injury. Forty-nine rabbits subjected to 30 min of coronary occlusion and 120 min of reperfusion were randomized into five groups: VEH (n = 11) received saline vehicle; IR (n = 9) received an infusion of cloricromene starting at the onset of ischemia at 8 micrograms.kg-1.min-1; R(-5)(n = 9) and R(+30)(n = 9) received an infusion of cloricromene at 8 micrograms.kg-1.min-1 starting 5 min before reperfusion and 30 min after reperfusion, respectively; and RB(-5)(n = 11) received 300 micrograms/kg bolus of cloricromene 5 min before reperfusion followed by an infusion of 8 micrograms.kg-1.min-1. All infusions were continued until the end of the reperfusion period. Myocardial infarct size was significantly reduced in groups IR, R(-5), and RB(-5). We conclude that cloricromene's effective time of action occurs prior to the first 30 min of the reperfusion period.

Animals↗
PubMed1997

Renal dose dopamine does not alter the response to beta-adrenergic stimulation by isoproterenol in healthy human volunteers.

OBJECTIVES: To determine if renal dose dopamine (3 microg/kg/min) alters the heart rate (HR) by itself, or if a dopamine infusion alters the HR response to bolus doses of the beta-adrenergic agonist isoproterenol in healthy human subjects. DESIGN: Prospective study. SETTING: Clinical laboratory of a university-affiliated academic medical center. SUBJECTS: A total of 15 healthy nonpregnant women and men aged 21 to 44 years. INTERVENTIONS: Subjects were monitored continuously with bedside ECG, pulse oximetry, and ambulatory ECG recording to measure the maximal HR response to separate injections of 10, 20, and 30 ng/kg of isoproterenol, given before, during, and after the infusion of 3 microg/kg/min of dopamine. MEASUREMENTS AND MAIN RESULTS: Dopamine in the absence of isoproterenol did not alter baseline HR significantly (62.7+/-2.2 beats/min without dopamine; 65.4+/-2.2 with dopamine; p=0.15). All three doses of isoproterenol increased HR significantly above baseline, both in the presence and absence of dopamine (p<0.001). Dopamine infusion resulted in a higher HR following isoproterenol only for the 20-ng/kg dose. The incremental increases in HR, defined as the difference between peak HR following isoproterenol and baseline HR, were not increased during dopamine infusion for any of the doses of isoproterenol. Nausea was reported by 5 of the 15 subjects during the dopamine infusion. CONCLUSIONS: In healthy human subjects, infusion of 3 microg/kg/min of dopamine does not significantly increase the HR when combined with beta-adrenergic stimulation using isoproterenol, suggesting neither an additive nor antagonistic interaction between the two drugs. While our study did not demonstrate an increase in HR in healthy subjects, the risk of increasing the chronotropic response to beta-adrenergic inotropic medications with "renal dose" dopamine in critically ill patients needs to be investigated. The frequency of nausea during dopamine infusion also may influence consideration of using dopamine to augment splanchnic blood flow and renal function in conscious patients.

Adrenergic beta-Agonists↗
PubMed1997

The effect of esmolol on ST-segment depression and arrhythmias after electroconvulsive therapy.

Electroconvulsive therapy (ECT) induces sympathetically mediated hemodynamic alterations that can be associated with myocardial ischemia and arrhythmia generation. Esmolol, a short-acting beta-blocker, blunts the hypertension and tachycardia seen with ECT. The purpose of this study is to determine whether esmolol use during ECT reduces the incidence of myocardial ischemia or arrhythmias after ECT. In a randomized, double-blind, placebo-controlled protocol, with each patient acting as his/her own control, the effects of esmolol on the incidence of myocardial ischemia and arrhythmias were studied using two-lead Holter monitoring for at least 2 h post-ECT. Nineteen patients underwent 71 ECT treatments (34 placebo, 37 esmolol), recording 746 h of Holter data. The esmolol group had significantly reduced heart rate and mean arterial pressure immediately after ECT. There was no difference in the incidence of ECG defined ischemia post-ECT between groups, with 7 of 19 (36.8%) patients in the esmolol group showing ST-segment depression compared with 5 of 19 (26.3%) in the placebo group. There was no difference between groups in arrhythmia detection. This experiment demonstrates that (a) ECT is associated with a significant incidence of ST-segment depression, (b) esmolol blunts the sympathetic discharge during ECT, and (c) esmolol does not reduce the incidence of post-ECT ischemia or arrhythmia.

Adrenergic beta-Antagonists↗
PubMed1996

The importance of the postoperative anesthetic visit: do repeated visits improve patient satisfaction or physician recognition?

This study evaluates whether repeated postoperative visits by the anesthesiologist improve patient ability to recall the anesthesiologist's name and the patient's perception of and satisfaction with anesthesia services. In a randomized, prospective trial, 144 patients with an anticipated postoperative length of stay of at least three days were enrolled in three groups: Group A patients (n = 48) had one postoperative visit, Group B (n = 48) had two postoperative visits, and Group C (n = 48) had three postoperative visits. All postoperative visits were performed by the attending anesthesiologist on consecutive postoperative days. Patients were contacted two days after their last postoperative visit to complete a study questionnaire. Patients were able to recall the anesthesiologist's name significantly less frequently than the surgeon's name, and there was no difference in name recall among groups. Recall was not affected by patient age, sex, or ASA physical status; the mode of contact (telephone versus personal visit); the anesthesiologist's gender; the presence of preoperative medication; or the identity of the preoperative evaluator. Patients could identify the anesthesiologist's gender approximately 85% of the time, regardless of group, and were more likely to identify female anesthesiologists (P = 0.026, odds ratio 3.3). Patient evaluation of hospital, surgical, and anesthesia care was favorable in all groups and did not vary with group. Increasing the number of postoperative visits does not improve patient name recognition of the anesthesiologist or increase patient satisfaction with or perception of anesthesia services.

Age Factors↗
PubMed1996

Relative efficacy and potency of beta-adrenoceptor agonists for generating cAMP in human lymphocytes.

BACKGROUND: Dopexamine and dobutamine are traditionally described as having primarily beta 2-adrenergic agonist properties; norepinephrine is generally classified as beta 1-selective; and epinephrine, isoproterenol, and dopamine are considered mixed beta 1- and beta 2-receptor agonists. Much of this selectivity is designated from studies conducted with intact cardiovascular systems in which indirect actions (eg, norepinephrine release from presynaptic nerve terminals) are not separated from direct agonist-receptor interactions. OBJECTIVE: To assess the relative efficacy and potency of dopamine, dobutamine, dopexamine, epinephrine, isoproterenol, and norepinephrine for directly stimulating cyclic adenosine monophosphate (cAMP) production in human lymphocytes, a model of beta 2-adrenoceptor function. DESIGN: Open-label, prospective paired studies of lymphocytes from nine healthy human volunteers (seven men). SETTING: Experimental laboratory of a large, university-affiliated medical center. INTERVENTIONS: Concentration-response curves were generated for each adrenergic agonist; maximal cAMP production was used to compare efficacy. For the agonists that more than doubled basal cAMP concentrations, EC50 calculations were used to compare potency. MEASUREMENTS AND MAIN RESULTS: Isoproterenol and epinephrine produced the greatest concentrations of cAMP of the agonists tested. cAMP production was increased by isoproterenol at concentrations 1/10 to 1/10,000 that of the other agonists. Norepinephrine stimulated cAMP production only one third as much as epinephrine and isoproterenol, but more than double the level of dopamine, dobutamine, and dopexamine. EC50 concentrations for norepinephrine were 10-fold higher than epinephrine and 50-fold higher than isoproterenol. CONCLUSIONS: Epinephrine and isoproterenol are the most efficacious and potent direct-acting beta 2-adrenergic receptor agonists using this lymphocyte cAMP model. Norepinephrine exhibits significant effects on the beta-receptors on lymphocytes, suggesting beta 2-adrenoceptor effects with high concentrations of this drug. The very low cAMP levels generated by dopamine, dobutamine, and dopexamine (even in high concentrations) support other evidence that these agents have little direct effect on the beta 2-adrenoceptor.

Adrenergic beta-Agonists↗
PubMed1995

A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults undergoing cardiac surgery.

Milrinone can reverse acute postischemic myocardial dysfunction after cardiopulmonary bypass, although neither the appropriate bolus dose nor its pharmacokinetics has been established for cardiac surgical patients. Consenting patients undergoing cardiac surgery received milrinone (25, 50, or 75 micrograms/kg) in an open-label, dose-escalating study if their cardiac index was < 3 L.min-1.m-2 after separation from bypass. Heart rate, mean arterial blood pressure, pulmonary capillary wedge pressure, and cardiac index were determined before and after the administration of milrinone. Timed blood samples were obtained for measurement of milrinone plasma concentrations and pharmacokinetic analysis. Twenty-nine of 60 consenting patients had cardiac indices < 3 L.min-1.m-2 after separation from bypass, received milrinone, and completed the protocol. All three bolus doses of milrinone significantly increased cardiac index. The 50- and 75-micrograms/kg doses produced significantly larger increases in cardiac index than the 25-micrograms/kg dose; however, the 75-micrograms/kg dose did not produce a significantly larger increase in cardiac index than did the 50-micrograms/kg dose. Two of 10 patients receiving milrinone 25 micrograms/kg, but no patient receiving either 50 or 75 micrograms/kg, required early epinephrine rescue when the cardiac index failed to increase by > 15%. The 75-micrograms/kg dose was associated with a case of ventricular tachycardia. The three-compartment model better described milrinone drug disposition than the two-compartment model by both visual inspection and Schwartz-Bayesian criterion. There was only limited evidence of dose-dependence, so data from all three doses are reported together (and normalized to the 50-micrograms/kg dose). Data from one patient was discarded (samples mislabeled). Using mixed-effects nonlinear regression (for n = 28), the following volumes were determined for the three compartments: V1 = 11.1 L, V2 = 16.9 L, and V3 = 363 L. Similarly, the following clearances were estimated for the three compartments: Cl1 = 0.067 L/min, Cl2 = 1.05 L/min, and Cl3 = 0.31 L/min. The 50-micrograms/kg loading dose appeared more potent than the 25-micrograms/kg dose, and, as potent, but with possibly fewer side-effects than the 75-micrograms/kg dose. The short context-sensitive half-times of 6.7 or 10.2 min after 1- or 10-min bolus infusions underscore the need for prompt institution of a maintenance infusion when milrinone concentrations must be maintained.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Triiodothyronine increases contractility independent of beta-adrenergic receptors or stimulation of cyclic-3',5'-adenosine monophosphate.

BACKGROUND: Triiodothyronine regulates cardiac contractility; however, the mechanisms by which it produces its acute contractile effects remains unknown. We compared the acute effects of thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) and of isoproterenol on the contractility of isolated rat hearts. In addition, we sought to determine whether the acute inotropic effects of thyroid hormones were mediated by beta-adrenergic receptors or by increased production of cyclic-3',5'-adenosine monophosphate (cAMP). METHODS: A Langendorff heart preparation harvested from euthyroid male Sprague-Dawley rats was used. Drugs were administered through an aortic perfusion catheter. A pressure-transduced left-ventricular balloon catheter measured pressure and heart rate changes. Changes in the maximum positive rate of change in pressure (dP/dT) and maximum negative dP/dT were determined. Responses to varying doses of T3, T4, and isoproterenol were assessed in the presence and absence of beta-adrenergic receptor blockade with propranolol. cAMP production, measured by radioimmunoassay, was determined in myocardial cell suspensions after incubation with T3 or isoproterenol. RESULTS: T3 0.74 nmol rapidly and significantly increased maximum dP/dT by 335 +/- 38 mmHg/s within 30 s after bolus injection; however, contractility was unchanged after as much as 12.9 nmol T4. The maximal increase in dP/dT after 0.8 nmol isoproterenol was comparable to that produced by T3. However, the cardiotonic actions of isoproterenol were significantly slower to develop (peaking at 60 vs. 15 s) and lasted longer than those of T3. Pretreatment with propranolol 1 mumol diminished the contractile effects of isoproterenol but had no effect on those of T3. Concentrations of isoproterenol that increase contractility also significantly increased cAMP production in isolated rat myocardial cells. However, T3 failed to increase cAMP production. CONCLUSIONS: These results demonstrate that the acute inotropic effects of T3 are not shared by T4 and appear unrelated to beta-adrenergic receptor mechanisms or to generation of cAMP. Thus, T3 acutely stimulates cardiac contraction by mechanisms that differ from those of the more commonly used beta-adrenergic receptor agonists and phosphodiesterase inhibitors. Further studies are needed to identify the mechanisms underlying the acute contractile effects of T3 and to determine whether T3 will prove useful for increasing ventricular function in patients.

Adrenergic beta-Antagonists↗