Robert J. Deegan

Optimization of high-performance liquid chromatographic assay for catecholamines: Determination of optimal mobile phase composition and elimination of species-dependent differences in extraction recovery of 3,4-dihydroxybenzylamine

This paper describes the application of a window diagram technique to optimize the four components of eluent (sodium acetate, sodium heptanesulfonate, acetonitrile and pH adjusted by monochloroacetic acid), for complete separation of five catecholamine compounds and the internal standard (3,4-dihydroxybenzylamine, DHBA). In addition, studies were performed to address the problem of the variable recovery of DHBA from dog plasma due to a time-dependent loss of DHBA. We found that this phenomenon can be prevented by pH adjustment prior to addition of DHBA, allowing development of an accurate high-performance liquid chromatographic assay for plasma catecholamines in dogs.

β‐Adrenergic receptor—mediated release of norepinephrine in the human forearm

Because of difficulties in separating the systemic from local effect, the role of presynaptic β2‐adrenergic receptors in facilitating the neural release of norepinephrine has not been defined previously in humans in vivo. To determine whether stimulation of presynaptic β‐receptors alters local release of norepinephrine, we examined the effects on norepinephrine kinetics of 60 and 400 ng/min intra‐arterial isoproterenol in seven healthy male volunteers. Isoproterenol, 60 ng/min, increased forearm norepinephrine spillover sixfold from a baseline spillover of 0.45 ± 0.08 to 2.89 ± 0.69 ng/min (p < 0.01), whereas 400 ng/min isoproterenol increased forearm norepinephrine spillover to 13.25 ± 2.49 ng/min (p < 0.005), a 29‐fold increase above baseline. Coinfusion of 20 to 40 µg/min propranolol with 400 ng/min isoproterenol in four subjects significantly attenuated the isoproterenol‐induced increase in local norepinephrine spillover to 2.09 ± 0.92 ng/min (p < 0.05 versus 400 ng/min isoproterenol). This study shows that presynaptic ß‐adrenergic receptors facilitate local release of norepinephrine in vivo in humans.

In-hospital outcomes of a minimally invasive off-pump left thoracotomy approach using a centrifugal continuous-flow left ventricular assist device

BACKGROUND Minimally invasive left thoracotomy (MILT) and off-pump implantation strategies have been anecdotally reported for implantation of the HeartWare ventricular assist device (HVAD). We analyzed our experience with off-pump MILT implantation techniques and compared early in-hospital outcomes with conventional on-pump sternotomy (CS) implantation strategy. METHODS Between January 2013 and February 2014, 51 patients underwent HVAD implantation and were included in this study. Thirty-three patients had CS, whereas 18 patients underwent off-pump MILT. To compare outcomes of these techniques, a multivariate analysis using propensity score modeling was performed after adjusting for age, INTERMACS, Kormos and Leitz-Miller (LM) scores. RESULTS Mean age at implant was 57 (range 18 to 69) years, and overall in-hospital mortality was 8%. Univariate analysis revealed a statistically significant reduction in days on inotropes (p = 0.04), and a trend toward reduced intra-operative blood product administration (p = 0.08) in the MILT group. There was no difference in intensive-care-unit length of stay (p = 0.5), total length of stay (p = 0.76), post-operative blood product administration (p = 0.34) and total time on mechanical ventilation (p = 0.32). After adjusting for age, INTERMACS profile and Kormos and LM scores, no statistically significant differences were observed between the MILT and CS groups. CONCLUSIONS An off-pump MILT implantation strategy can be utilized as a safe surgical approach for patients undergoing HVAD implantation. Further large collaborative studies are needed to identify advantages of the MILT approach.

Effects of anesthesia on norepinephrine kinetics. Comparison of propofol and halothane anesthesia in dogs.

Alteration of sympathetic function is a major determinant of the cardiovascular effects of anesthetic agents. Plasma norepinephrine (NE) concentrations are determined not only by the rate of NE release from sympathetic nerves but also by NE clearance rate. Therefore, NE concentration in plasma may be an inadequate index of sympathetic activity. We used an isotope dilution technique to investigate the effects of halothane and propofol anesthesia on NE kinetics. A relationship of NE kinetics to halothane dose was determined in six dogs. Halothane 1.0 MAC reduced plasma NE concentration by 35 +/- 9% versus awake (P less than 0.05). This was due to a reduction of 52 +/- 9% in NE spillover (P less than 0.05) accompanied by a reduction of 27 +/- 5% in NE clearance (P less than 0.005). The clearance changes were dose-dependent: reductions were 34 +/- 4% at 1.5 MAC (P less than 0.05 vs. 1.0 MAC) and 45 +/- 5% at 2.0 MAC (P less than 0.05 vs. 1.5 MAC). Six dogs were studied with a single halothane dose (1.0 MAC) and NE concentration, spillover, and clearance were found to be stable over a period of 5.5 h of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Long‐term exposure to β2‐receptor agonist specifically desensitizes β‐receptor—mediated venodilation

Desensitization of human vascular smooth muscle has not been shown after long‐term exposure to agonist. Using the dorsal hand vein compliance technique, we measured the vascular sensitivity to isoproterenol, alprostadil, and nitroglycerin. Nine volunteers were studied after receiving no treatment or after 7 days of the β2‐agonist terbutaline (5 mg three times daily). Terbutaline pretreatment desensitized the vascular response to isoproterenol, resulting in a fourfold increase in the dose of isoproterenol required to produce 10% vasodilation (geometric mean after terbutaline, 100.8 ng/min; without terbutaline, 26.7 ng/min; p < 0.001). The desensitization was specific for β2‐receptor—mediated effects. We have therefore shown that dynamic regulation of vascular responsiveness by long‐term exposure to β2‐receptor agonist occurs in humans. This selective desensitization of vascular β‐adrenergic responsiveness will result in mixed α‐ and β‐adrenergic agonists, such as epinephrine, becoming relatively more vasoconstrictive, and it also has important implications in blood pressure response to stress.

β‐Receptor antagonism does not fully explain esmolol‐induced hypotension

Esmolol is an ultra‐short‐acting β‐blocker that is widely used to lower blood pressure in acute settings intraoperatively and in patients with hypertension. Other β‐blockers have not been used in this way because of the belief that β‐blockers do not acutely lower blood pressure. The purpose of this study was to determine if esmolol has a hypotensive effect that is greater than other β‐blockers at similar degrees of β‐blockade. Esmolol, metoprolol, and propranolol were administered intravenously at three doses chosen to produce comparable degrees of β‐blockade. In spite of achieving comparable β‐blockade, esmolol produced a greater reduction in blood pressure than the other β‐blockers, implying that the hypotensive effect of esmolol cannot be accounted for simply by β‐blockade. There was no evidence to support a direct vasodilatory action of esmolol, and esmolol did not lower plasma norepinephrine concentrations.

Takotsubo Cardiomyopathy and Coronary Vasospasm During Orthotopic Liver Transplantation: Separate Entities or 'Common Mechanism?

l AKOTSUBO CARDIOMYOPATHY (idiopathic or transient left ventricular apical ballooning syndrome [ABS]) is reversible condition frequently precipitated by a stressful rigger that clinically mimics an acute ST-elevation myocardial nfarction.1 Characteristically, hypokinesis or akinesis occurs in he mid and apical segments of the left ventricle in the absence f epicardial coronary lesions. Preserved (or hyperdynamic) unction of the basal myocardial segments results in apical allooning, assuming the shape of a Japanese pot used to catch ctopus (a takotsubo). This syndrome has been reported in the perioperative setting fter both minor and major (eg, orthotopic liver transplantation) urgical procedures.2-4 Intraoperatively, ABS manifests as cariogenic shock and is displayed as ST-elevation on an electroardiogram (ECG) without angiographic evidence of coronary cclusion.5 Coronary vasospasm has also been described as a eparate entity during liver transplantation, with similar clinical igns also representative of an acute myocardial infarction.2,6,7 he authors report a patient presenting intraoperatively with imultaneous severe right coronary artery (RCA) vasospasm nd ABS during liver transplant surgery.

Cardiovascular Manifestations of Endocrine Dysfunction

c f ENDOCRINOPATHIES may have a significant impact on the cardiovascular system. The effects may be humoral or structural and may contribute to significant morbidity and mortality. This article examines and specifically focuses on the cardiovascular manifestations of thyroid dysfunction, acromegaly, pheochromocytomas, neuroendocrine tumors, and adrenal cortical dysfunction in addition to the cardiovascular effects of exogenously administered androgenic anabolic steroids. Diabetes mellitus, which has been covered extensively elsewhere, is not included in this review. For discussion of the cardiovascular manifestations of that condition, as well as for general information regarding the perioperative management of patients with endocrine diseases, the reader is referred to standard reference texts and general literature reviews.1,2

Extending the use of the pacing pulmonary artery catheter for safe minimally invasive cardiac surgery.

OBJECTIVE In this study, the therapeutic use of pacing pulmonary artery catheters in association with minimally invasive cardiac surgery was evaluated. DESIGN A retrospective study. SETTINGS A single institutional university hospital. PARTICIPANTS Two hundred twenty-four consecutive patients undergoing minimally invasive cardiac surgery through a small (5-cm) right anterolateral thoracotomy using fibrillatory arrest without aortic cross-clamping. MEASUREMENTS AND MAIN RESULTS Two hundred eighteen patients underwent mitral valve surgery (97%) alone or in combination with other procedures. Six patients underwent other cardiac operations. In all patients, the pacing pulmonary artery catheter was used intraoperatively to induce ventricular fibrillation during the cooling period, and in the postoperative period it also was used in 37 (17%) patients who needed to be paced, mainly for bradyarrhythmias (51%). There were no complications related to the insertion of the catheters. Six (3%) patients experienced a loss of pacing capture, and 2 (1%) experienced another complication requiring the surgical removal of the catheter. Seven (3%) patients needed postoperative implantation of a permanent pacemaker. CONCLUSIONS In combination with minimally invasive cardiac surgery, pacing pulmonary artery catheters were therapeutically useful to induce ventricular fibrillatory arrest intraoperatively and for obtaining pacing capability in the postoperative period. Their use was associated with a low number of complications.

Regulation of Norepinephrine Release by β2-adrenergic Receptors during Halothane Anesthesia

Background Presynaptic receptors control norepinephrine (NE) release. It has been hypothesized that epinephrine stimulates prejunctional beta2-adrenergic receptors to facilitate NE release from sympathetic nerve endings, and therefore, pre-synaptic receptors controlling NE release are potential therapeutic targets to limit the adverse effects of excess sympathetic stimulation during anesthesia. We have previously demonstrated beta2-adrenergic receptor-augmented release of NE in the human forearm and have shown that halothane inhibits sympathetic activity in vivo by decreasing the NE spillover rate into plasma. The goal of the current study was to determine the effect of halothane on beta2-adrenergic receptor-augmented NE release in a canine hind-limb experimental model. Methods Seven female dogs were studied awake and during halothane anesthesia (1.0 minimum alveolar concentration). A trace dosage of [sup 3 Hydrogen]NE (15 micro Ci over a 1-min period and 0.6 micro Ci/min thereafter) was infused into the femoral vein. Before and during femoral arterial administration of isoproterenol at two dosages (30 and 80 mg/min), hind-limb blood flow was measured by an ultrasonic flow probe and hind-limb NE spill-over by an isotope dilutional technique. Results In awake dogs, isoproterenol significantly increased hind-limb blood flow and NE spillover into the hind limb. Halothane had no effect on baseline or isoproterenol-stimulated hind-limb blood flow (a postjunctional beta2 effect) but significantly inhibited the isoproterenol-induced increase in hind-limb NE spillover (a prejunctional beta2 effect). Conclusions The isoproterenol-mediated increase in NE release is inhibited by halothane anesthesia, indicating that halothane inhibits prejunctional beta2-adrenergic receptor regulation of NE release.