Catecholamine Stress Research Articles

K + transport and energetics in Kir6.2 −/− mouse hearts assessed by 87Rb and 31P magnetic resonance and optical spectroscopy

Cardiac sarcolemmal K ATP channels are crucial in adaptation to stress caused by metabolic inhibition and moderate exercise, which requires not only down-regulation of energy spending, but also up-regulation of mitochondrial ATP synthesis. To investigate sarcolemmal and mitochondrial effects of a Kir6.2 (K + ion-selective subunit of the channel) knockout, we used non-invasive techniques ( 87Rb, 31P NMR and optical spectroscopy) to study (1) K + fluxes, (2) high-energy phosphates, (3) the cytochrome c oxidase redox state, (4) myoglobin deoxygenation, and (5) contractile function at the baseline and in response to metabolic uncoupling with 2,4-dintrophenol (DNP) and stimulation with isoproterenol in Langendorff-perfused mouse hearts. Comparison with control C57BL6 hearts demonstrated that the Kir6.2 knockout resulted in: (a) a lack of stimulation of the unidirectional potassium efflux from the hearts when K ATP channels were activated metabolically by DNP (50 μM, 20 min); (b) a decrease in ATP, but not phosphocreatine, at the baseline, that became even more pronounced when the hearts were subjected to stress due to metabolic inhibition or increased workload caused by isoproterenol infusion (0.1 μM, 20 min); (c) significantly higher reduction of cytochrome c oxidase in response to DNP uncoupling; (d) a blunted response to isoproterenol stimulation. Thus Kir6.2 knockout is associated with decreased tolerance of mouse hearts to metabolic inhibition and catecholamine stress.

Haemodynamic and catecholamine stress responses to the Laryngeal Tube‐Suction Airway and the Proseal Laryngeal Mask Airway

Supraglottic airway devices such as the ProSeal Laryngeal Mask Airway (PLMA) and Laryngeal Tube-Suction Airway (LTS) that provoke the least stress responses could be beneficial in many situations, especially in patients with cardiovascular disease. We compared the haemodynamic and catecholamine stress response of the LTS and PLMA in a randomised study of 36 patients. Mean arterial pressure, heart rate, epinephrine and norepinephrine levels were all reduced following induction of anaesthesia with no significant differences between the two groups. Following insertion of LTS, mean arterial pressure, heart rate, epinephrine and norepinephrine levels increased to pre-induction levels. However, following the insertion of the PLMA, mean arterial pressure, heart rate, epinephrine and norepinephrine levels remained significantly lower than pre-induction values. Mean arterial pressure, heart rate and epinephrine were significantly greater in the LTS group than in the PLMA group. We conclude that the LTS produces a greater and more sustained haemodynamic and catecholamine stress response than does the PLMA.

Transplantation of human umbilical vein endothelial cells improves left ventricular function in a rat model of myocardial infarction

Although cell-based therapy after myocardial infarction (MI) may be beneficial in improving cardiac dysfunction, the underlying mechanisms remain to be clarified. Since human umbilical vein endothelial cells (HUVEC) harbor the potential for transdifferentiation, we studied the functional effects of HUVEC transplantation in a rat model of MI. HUVEC labeled with BrdU or medium alone were injected into the infarcted area and its margin 4 weeks after ligation of the left coronary artery in cyclosporine-treated rats. BrdU(+) signals could be detected in the area of MI at two weeks and two months after injection only in hearts transplanted with HUVEC. While no signs of transdifferentiation into cardiomyocytes were evident, staining for the rat macrophage marker ED-1, adjacent to or colocalized with BrdU(+) signals, revealed an in.ltration with macrophages and implied the phagocytosis of injected HUVEC. In the vicinity of BrdU(+) signals, the density of CD31(+) microvessels was significantly increased in HUVEC-transplanted as compared to medium-treated hearts after two months. HUVEC transplantation led to improved contractility as assessed by echocardiography and to higher coronary flow rates as well as to improved response to volume strain and catecholamine stress in Langendorff perfused hearts. After MI, transplanted HUVEC persist in the host myocardium and trigger an infiltration with macrophages. The ensuing increase in neovascularization and improvement in global left ventricular function may be attributable to the associated inflammatory response.

Genetic knockout of KATP channels predisposes to catecholamine-induced proarrhythmogenesis

Cardiac K-ATP channels have been recently been implicated to serve a homeostatic function under catecholamine stress. Since the use of drugs that modulate K-ATP channels is common in clinical practice, the implications of channel function on cardiac electrophysiology warrant further investigation. Here, using simultaneous monophasic action potential and ECG recordings, we examined the arrhythmogenic consequences of genetic deletion of the pore-forming K-ATP channel subunit Kir6.2. Infusion of the sympathomimetic isoproterenol (1muM) readily induced early afterdepolarizations in Kir6.2 knockout (KO) but not in the wildtype (WT) hearts (incidence: 96.8% versus 1%, p<0.01). This translated into an order of 10 magnitude higher incidence of triggered activity and associated premature ventricular contraction in the KO hearts. Although there was no significant difference in perfusion flow between KO and WT hearts before or after isoproterenol infusion, the shortening of the action potential duration at 90% repolarization under sympathomimetic challenge observed in the WT (from 82 to 74 ms, p<0.01) was absent in the KO (79 to 80 ms, p>0.05). We conclude that cardiac K-ATP channels are required to secure proper repolarization reserve and prevent afterdepolarization-associated arrhythmia under sympathetic stress. Therefore, clinical conditions that are associated with reduced K-ATP channel activity, such as use of sulfonylurea drugs, may predispose to arrhythmic events. Clinical Pharmacology & Therapeutics (2004) 75, P48–P48; doi: 10.1016/j.clpt.2003.11.181

Inhibition of receptor-localized PI3K preserves cardiac beta-adrenergic receptor function and ameliorates pressure overload heart failure.

beta-Adrenergic receptor (betaAR) downregulation and desensitization are hallmarks of the failing heart. However, whether abnormalities in betaAR function are mechanistically linked to the cause of heart failure is not known. We hypothesized that downregulation of cardiac betaARs can be prevented through inhibition of PI3K activity within the receptor complex, because PI3K is necessary for betaAR internalization. Here we show that in genetically modified mice, disrupting the recruitment of PI3K to agonist-activated betaARs in vivo prevents receptor downregulation in response to chronic catecholamine administration and ameliorates the development of heart failure with pressure overload. Disruption of PI3K/betaAR colocalization is required to preserve betaAR signaling, since deletion of a single PI3K isoform (PI3Kgamma knockout) is insufficient to prevent the recruitment of other PI3K isoforms and subsequent betaAR downregulation with catecholamine stress. These data demonstrate a specific role for receptor-localized PI3K in the regulation of betaAR turnover and show that abnormalities in betaAR function are associated with the development of heart failure. Thus, a strategy that blocks the membrane translocation of PI3K and leads to the inhibition of betaAR-localized PI3K activity represents a novel therapeutic approach to restore normal betaAR signaling and preserve cardiac function in the pressure overloaded failing heart.

Inhibition of receptor-localized PI3K preserves cardiac β-adrenergic receptor function and ameliorates pressure overload heart failure

β-Adrenergic receptor (βAR) downregulation and desensitization are hallmarks of the failing heart. However, whether abnormalities in βAR function are mechanistically linked to the cause of heart failure is not known. We hypothesized that downregulation of cardiac βARs can be prevented through inhibition of PI3K activity within the receptor complex, because PI3K is necessary for βAR internalization. Here we show that in genetically modified mice, disrupting the recruitment of PI3K to agonist-activated βARs in vivo prevents receptor downregulation in response to chronic catecholamine administration and ameliorates the development of heart failure with pressure overload. Disruption of PI3K/βAR colocalization is required to preserve βAR signaling, since deletion of a single PI3K isoform (PI3Kγ knockout) is insufficient to prevent the recruitment of other PI3K isoforms and subsequent βAR downregulation with catecholamine stress. These data demonstrate a specific role for receptor-localized PI3K in the regulation of βAR turnover and show that abnormalities in βAR function are associated with the development of heart failure. Thus, a strategy that blocks the membrane translocation of PI3K and leads to the inhibition of βAR-localized PI3K activity represents a novel therapeutic approach to restore normal βAR signaling and preserve cardiac function in the pressure overloaded failing heart.

Impaired Adaptative Responses to Catecholamine Stress in Aging Heart

Impaired Adaptative Responses to Catecholamine Stress in Aging Heart

Stress hormones during the wake-up test in scoliosis surgery

Study objective To compare hemodynamic and endocrine stress responses of two anesthetic regimes during intraoperative wake-up tests in scoliosis surgery. Design Randomized, controlled clinical study. Setting University hospital. Patients 40 ASA physical status I and II teenage patients scheduled for scoliosis surgery. Intervention Patients were randomly divided into two groups: the propofol group (Group P) and the sevoflurane group (Group S). In Group P, anesthesia was induced with propofol and remifentanil and was maintained with infusions. Sevoflurane and remifentanil were used in Group S. After surgical instrumentation, patients were awakened, and the wake-up times were recorded. To determine the stress responses, blood samples were taken before induction, 10 minutes after surgical incision, before the wake-up test, during the wake-up test, and 10 minutes after the wake-up test. Cortisol, epinephrine, and norepinephrine concentrations, and hemodynamics all were recorded at the same time. Measurements and main results The times from discontinuation of anesthetics to eye opening and movement were similar in both groups. Epinephrine and norepinephrine concentrations during the wake-up test were significantly higher than pretest results in both groups ( p < 0.001). There were no statistically significant differences between groups in heart rate or blood pressure. Conclusions Propofol-remifentanil anesthesia is equivalent to sevoflurane-remifentanil anesthesia for a wake-up test. Both the propofol- and sevoflurane-based anesthetic regimens abolish hemodynamic and endocrine stress responses to incision for scoliosis surgery in teenagers. Intraoperative wake-up testing is associated with substantial catecholamine stress despite virtually unchanged mean arterial pressure and heart rate.

Catecholamine-Induced T-Wave Lability in Congenital Long QT Syndrome: A Novel Phenomenon Associated With Syncope and Cardiac Arrest

To determine the effects of phenylephrine and dobutamine on repolarization lability in patients with genotyped long QT syndrome (LQTS). Between December 1998 and August 2000, 23 patients with genotyped LQTS (13 LQT1, 7 LQT2, and 3 LQT3) and 16 controls underwent electrocardiographic stress testing at the Mayo Clinic in Rochester, Minn. Aperiodic repolarization lability was quantified from digitized electrocardiograms recorded during catecholamine stress testing with phenylephrine and dobutamine. T-wave lability was quantified as a root-mean-square of the differences between corresponding signal values of subsequent beats. The magnitude of aperiodic T-wave lability was quantified by using a newly derived T-wave lability index (TWLI). The TWLI was significantly greater in patients with LQTS than in controls (0.0945 +/- 0.0517 vs 0.0445 +/- 0.0123; P < .003). Marked T-wave lability (TWLI > or = 0.095) was detected in all 3 LQTS genotypes (10/23) but in no controls (P < .003). There was no correlation between the TWLI and the baseline corrected QT interval. All high-risk patients having either a history of out-of-hospital cardiac arrest or syncope had a TWLI of 0.095 or greater. Beat-to-beat nonalternating T-wave lability occurs in LQT1, LQT2, and LQT3 patients during catecholamine provocation and is associated with a history of prior cardiac events. The quantification of this novel phenomenon may assist in identifying LQTS patients with increased risk of sudden cardiac death.

Hemodynamic and Catecholamine Stress Responses to Insertion of the Combitube®, Laryngeal Mask Airway or Tracheal Intubation

Hemodynamic and Catecholamine Stress Responses to Insertion of the Combitube®, Laryngeal Mask Airway or Tracheal Intubation

Preface

We observed that heterozygous knockout (+/-, KO) of either endothelin-A- (ET(A)) or -B- (ET(B)) receptors significantly reduced the pressor responses to systemically administered endothelin-1 (ET-1) in ET(A) or ET(B) (+/-) KO mice when compared to wild-type (WT) mice (data not shown). Also, we observed that basal mean arterial pressure (MAP) is significantly higher in ET(B) (+/-) (92.7 +/- 1.2 mmHg) (n = 53, p < 0.05) but not ET(A) (+/-) KO mice (70.6 +/- 1.8 mmHg) (n = 23) when compared to their anaesthetized WT littermates (70.1 +/- 0.7 mmHg) (n = 118). A 90 min treatment with either BQ-123 (10 mg/kg), an ET(A)-selective antagonist, or BQ-928 (10 mg/kg), a mixed ET(A)/ET(B) antagonist, administered intraperitoneally, significantly reduced basal MAP of ET(B) (+/-) KO mice almost to the level of their WT treated counterparts (94.9 +/- 4.9 mmHg) (n = 6) vs (+ BQ-123: 59.7 +/- 0.3 mmHg, n = 8); (+ BQ-928: 72.4 +/- 2.6 mmHg, n = 5). It is worthy of note that BQ-123 significantly reduced basal MAP in WT mice but to a lesser extent than in ET(B) (+/-) KO mice (69.6 +/- 2.3 mmHg, n = 8) vs (+ BQ-123: 57.3 +/- 1.4 mmHg, n = 8). In contrast, the ET(B)-selective antagonist, BQ-788 (10 mg/kg i.p.), had no significant effect on MAP even after 90 min of treatment (ET(B) (+/-) KO: (92.3 +/- 2.3 mmHg, n = 6) vs (+ BQ-788: 89.7 +/- 3.1 mmHg, n = 6); WT: (70.5 +/- 3.7 mmHg, n = 7) vs (+ BQ-788: 71.2 +/- 2.0 mmHg, n = 6). Therefore heterozygous KO of either ET(A)- or ET(B)-receptors significantly alters the phenotypic pressor properties of ET-1. We also suggest that there is less ET clearance in ET(B) (+/-) KO mice than in WT mice, which can explain the ET(A)-dependent hypertensive state of the former strain.

Hemodynamic and Catecholamine Stress Responses to Insertion of the Combitube[registered sign], Laryngeal Mask Airway or Tracheal Intubation

In a prospective, randomized, and controlled trial, we compared the stress responses after insertion of the Combitube[registered sign] (CT; Kendall-Sheridan Catheter Corp., Argyle, NY), the laryngeal mask airway (LMA), or endotracheal intubation (ET). Seventy-five patients scheduled for routine urological or gynecological surgery were randomly allocated to one of three groups and were ventilated via either an ET, a LMA, or a CT. All three devices could be inserted easily and rapidly, providing adequate ventilation and oxygenation. Insertion of the CT was associated with a significant increase in mean maximal systolic arterial pressure (160 +/- 32 mm Hg) and diastolic arterial pressure (91 +/- 17 mm Hg) compared with ET (140 +/- 24, 78 +/- 11 mm Hg; P < 0.05, P < 0.01, respectively) or insertion of the LMA (115 +/- 33, 63 +/- 22 mm Hg, both P < 0.001). The mean maximal epinephrine and norepinephrine plasma concentrations after insertion of the CT (37.3 +/- 31.1 and 279 +/- 139 pg/mL, respectively) were significantly higher than those after ET (35.8 +/- 89.8 and 195 +/- 58 pg/mL, respectively) or insertion of a LMA (17.3 +/- 13.3 and 158 +/- 67 pg/mL, respectively). This might be attributed to the pressure of the pharyngeal cuff of the CT on the anterior pharyngeal wall. We conclude that insertion of the CT causes a pronounced stress response and that precautions should be taken when used in patients at risk of hypertensive bleeding. Implications: In this study, we showed that the hemodynamic and catecholamine stress responses after insertion of the Combitube[registered sign] (Kendall-Sheridan Catheter Corp., Argyle, NY) were significantly higher compared with laryngeal mask airway or endotracheal intubation. We conclude that the increased stress response to insertion of a Combitube[registered sign] may represent a serious hazard to patients with cardiovascular disease. (Anesth Analg 1999;88:1389-94)

Blunted cardiovascular and catecholamine stress reactivity in women with bulimia nervosa

Cardiovascular and catecholamine responses to mental stressors were investigated in women with bulimia nervosa (BN) and in healthy control subjects. Fifteen women with BN and 15 control subjects completed psychosocial questionnaires before laboratory testing, where they were exposed to an interpersonally based speech stressor and a serial math task. Blood pressure, heart rate, epinephrine, norepinephrine and, via impedance cardiography, systolic time intervals, cardiac output and total peripheral resistance were measured at rest and during stress. Results indicated that BN was associated with blunted sympathetic activation in response to mental stress, indicated by increased pre-ejection period responses and blunted systolic blood pressure, heart rate and epinephrine responses. In contrast, women with BN had elevated cortisol levels when compared with control women. In addition, despite equivalent performance between groups, bulimic women reported feeling significantly more confused, frustrated, inadequate and dissatisfied with their performance during tasks. Psychosocial questionnaires also indicated that women with BN perceived more stress, had worse coping skills, lower self-esteem and sense of mastery, reported less social support, had worse mood, had greater anxiety and were more depressed when compared with control women. These results are interpreted as reflecting physiological and psychological profiles indicative of distress vs. active effort coping in BN. © 1998 Elsevier Science Ireland Ltd. All rights reserved.

Presence of a Severe Coronary Stenosis Augments Catecholamine Stress Induced Myocardial Preconditioning

Presence of a Severe Coronary Stenosis Augments Catecholamine Stress Induced Myocardial Preconditioning

Presence of a severe coronary stenosis augments catecholamine stress induced myocardial preconditioning

Presence of a severe coronary stenosis augments catecholamine stress induced myocardial preconditioning

Morbidity outcome in early versus conventional tracheal extubation after coronary artery bypass grafting: A prospective randomized controlled trial

Introduction: We undertook a prospective, randomized, controlled clinical trial to evaluate morbidity outcomes and safety of a modified anesthetic technique to provide shorter sedation and early extubation (1 to 6 hours) than those of the conventional anesthetic protocol used for prolonged sedation and extubation (12 to 22 hours) in patients after coronary artery bypass grafting. Methods: One hundred twenty patients undergoing elective coronary artery bypass grafting were prospectively assigned randomly to either an early extubation group ( n = 60; 15 μg·kg -1 fentanyl and 2 to 6 mg · kg -1· hour -1 propofol and isoflurane) or to a conventional extubation group ( n = 60; 50 μg·kg -1 fentanyl and 0.1 mg·kg -1 midazolam and isoflurane). Cardiac morbidity (postoperative myocardial ischemia, postoperative myocardial infarction, and perioperative sympathoadrenal stress response), respiratory morbidity (postextubation apnea, alveolar-arterial oxygen gradient, pulmonary shunting, oxygen consumption, atelectasis, and reintubation), hemodynamic values and vasoactive medication requirements, intraoperative awareness, postoperative cognitive function, 30 day mortality, and intensive care unit and hospital lengths of stay were compared between the two groups. Results: Fifty-one of the 60 patients in each group (85%) were extubated within the defined time period. Postoperative extubation time and intensive care unit and hospital lengths of stay were significantly shorter in the early group. At 48 hours after operation, there were no significant differences between the two groups in myocardial ischemia incidences, ischemia burdens, or creatine kinase isoenzyme MB levels. Four patients in the conventional group, but not in the early group, had postoperative myocardial infarction. The extubation anesthetics used were effective in suppressing the perioperative plasma catecholamine stress response in both groups. Postextubation apnea characteristics were similar between the groups. Intrapulmonary shunt fraction improved significantly in the early group at 4 hours after extubation. The incidences and degree of atelectasis did not differ significantly between the two groups. The incidences of treated postoperative complications were comparable between the two groups, but three patients in the conventional group died as a result of stroke or postoperative myocardial infarction. Conclusion: Early extubation after coronary artery bypass grafting is safe and does not increase perioperative morbidity. There is an improvement in postextubation intrapulmonary shunt fraction and a reduction in intensive care unit and hospital lengths of stay. (J T HORAC C ARDIOVASC S URG 1996;112:755-64)

Effect of the season on lipid peroxidation in the myocardium of rats with different resistance to hypoxia

Lipid peroxidation and the antioxidant system of the myocardium of adult male Wistar rats with low and high resistance to acute hypoxia tested by “raising” to an altitude of 11.5 km are studied in winter and in summer. It is found that the winter season is a mild stressor inducing changes in the myocardial antioxidant system and lipid peroxidation which are similar to those observed at the early stages of catecholamine stress in the summer season. In both cases alterations are more pronounced in low-resistance than in high-resistance rats. In winter, in low-resistance rats the intensity of lipid peroxidation and the activity of the antioxidant system are lower, while the ratio of their parameters (chemiluminescence data) is higher. At the same time, the levels of thiobarbituric acid-reactive substances are higher in winter in both groups. The relationship between the studied parameters and the resistance of rats to hypoxia is more obvious in winter than in summer, i.e., it is season-dependent and is also more pronounced in catecholamine stress.

Downregulation of Thyroid Hormone Receptor Subtype mRNA Levels by Amiodarone during Catecholamine Stress in Vitro

Amiodarone, a powerful antiarrhythmic drug, likely exerts its major effect by antagonism of thyroid hormone (T3), probably at the receptor level. T3 is known to regulate β-adrenergic receptor density in the heart but the effects of sympathomimetic drugs on thyroid hormone receptors (T3R) is not known. The aim of this study was to investigate how amiodarone and isoproterenol affect T3R-mRNA in cultured cardiomyocytes. Confluent, isoproterenol pretreated, AT-1 cardiomyocytes were treated with isoproterenol free medium, amiodarone, T3 and amiodarone together with T3 for 48 hours. Solution hybridization for the determination of mRNA for T3R α1, α2, β1 and β2 were performed. In itself isoproterenol upregulated T3R α1, T3R β1, T3R β2 (p<0.05), but did not affect the levels of T3R α2. Amiodarone and T3, respectively, downregulated T3R α1, T3R β1, T3R β2 (p<0.05), but did not affect the levels of T3R α2. Amiodarone and and T3, added together, upregulated T3R α2 and T3R β1 (p<0.05) as compared to amiodarone or T3 alone. There was an antagonistic effect between amiodarone and T3 for the regulation T3R β1. This is the first evidence showing that amiodarone regulates T3R-mRNA concentrations during cathecholamine stress. Isoproterenol regulation of T3R-mRNA levels provides further evidence for the close interaction between the thyroid hormone and the β-adrenergic systems.

906-63 Quantitative Doppler Tissue Imaging for the Noninvasive Assessment of Left Ventricular Contractility

Doppler Tissue Imaging (DTI) is a new noninvasive imaging modality that allows direct quantitation of myocardial velocity. This study was designed to test the correlation of peak systolic myocardial velocities with other measures of left ventricular (LV) systolic function under conditions of varying contractility. Nine patients with mild or moderate mitral regurgitation (MR) and resting LV ejection fraction (EF) 14 to 70% (41.7 ± 22.2) underwent quantitative DTI of the inferoposterior mid-myocardium. LV dP/dt was estimated from the rate of change of MR velocity on continuous wave Doppler. LV EF, dP/dt and DTI peak systolic velocity (Vel) were measured both at rest and during dobutamine (Dobut) infusion (range 30 to 50 mcg/kg/min, mean 34 ± 7l, and evaluated for change (Δ) from baseline: Rest Dobut Δ p EF(%) 41.7 ± 22.2 56.6 ± 27.9 14.9 ± 8.3 0.001 DTI Vel (mm/s) 22.7 ± 4.2 35.3 ± 10.1 12.6 ± 8.7 0.004 dP/dt (mmHg/ms) 1050 ± 322 1766 ± 768 716 ± 622 0.01 Direct relationships existed between LV dP/dt and both EF (R = 0.78, P = 0.004) and DTI Vel (R = 0.81, P = 0.002). The change in dP/dt during dobutamine infusion compared to baseline exhibited a stronger correlation with change in DTI velocity (R = 0.77) than with change in ejection fraction (R = 0.35). We conclude that 1) both EF and peak systolic myocardial velocity are directly related to LV contractility measured by dP/dt, and 2) catecholamineinduced alteration in myocardial contractility is better reflected by changes in myocardial velocity than by changes in EF. Measurement of myocardial velocity using quantitative DTI may be useful in the noninvasive assessment of ventricular contractility, and may be a useful adjunct to echocardiographic wall motion analysis during catecholamine stress testing.

Characterization of arbutamine: A novel catecholamine stress agent for diagnosis of coronary artery disease

AbstractArbutamine, 1,2‐Benzenediol,4‐[1‐hydroxy‐2‐[[4‐(4‐hydroxyphenyl)butyl[amino]ethyl]rsqb;rsqb; hydrochloride, (R), is a new catecholamine being developed as a pharmacologic stress agent for the diagnosis of coronary artery disease and myocardial ischemia. The pharmacology of arbutamine was studied in vitro using receptor binding assays and functional bioassays of α‐ and β‐adrenoceptor activity, and in vivo using the hemodynamic responses to intravenous infusion in anesthetized and conscious dogs. In isolated membranes, receptor binding studies demonstrated Ki values of 196 ± 12 nM and 147 ± 11 nM for β1‐ and β2‐adrenoceptors, and 265 ± 4 nM and 867 ± 40 nM for α1‐ and β2‐adrenoceptors, suggesting that arbutamine is a mixed β1+2‐adrenoceptor agonist with significant affinity for β1‐adrenoceptors. This was supported by in vitro bioassay data, where arbutamine increased spontaneous atrial rate (β1‐activity, ED50 = 16 ± 6 nM), relaxed isolated tracheal rings (β2‐activity, ED50 = 13 ± 5 nM), and contracted aortic rings (α‐activity, ED50 = 430 ± 80 nM), indicating 25–30‐fold selectivity for β‐adrenoceptor activation. In conscious or anethetized dogs, arbutamine elicited dose‐dependent increases in heart rate and LV dP/dt with little fall in mean arterial pressure. The data demonstrate that arbutamine exhibits similar degrees of intropic and chronotropic activity, while eliciting less peripheral vasodialation than isoproteronal and less inotropic activity than dobutamine. Moreover, there was rapid termination of the tachycardia, as heart rate resolved to 50% of the maximal effect within 7.2 ± 1.1 min following arbutamine, compared to 5.5 ± 1.0 min following isoproterenol and 5.9 ± 1.4 min following dobutamine. This hemodynamic profile and rapid pharmacodynamic offset makes arbutamine ideally suited for use as a pharmacologic stress agent.