Timothy B. Curry

Sex Differences in Sympathetic Neural-Hemodynamic Balance Implications for Human Blood Pressure Regulation

Among young normotensive men, a reciprocal balance between cardiac output and sympathetic nerve activity is important in the regulation of arterial pressure. In young women, the balance among cardiac output, peripheral resistance, and sympathetic nerve activity is unknown. Consequently, the aim of this study was to examine the relationship of cardiac output and total peripheral resistance to muscle sympathetic nerve activity in young women. Multiunit peroneal recordings of muscle sympathetic nerve activity were obtained in 17 women (mean±SEM: age 24±3 years) and 21 men (mean±SEM: age 25±5 years). Mean resting muscle sympathetic nerve activity was lower in women compared with men (19±3 versus 25±1 bursts minute−1; P<0.05), as was mean arterial pressure (89±1 versus 94±2 mm Hg; P<0.05). Mean arterial pressure was not related to muscle sympathetic nerve activity in men (P=0.80) or women (P=0.62). There was a positive relationship between total peripheral resistance and muscle sympathetic nerve activity (r=0.62; P<0.05) and an inverse relationship between cardiac output and muscle sympathetic nerve activity (r=−0.69; P<0.05) in men. Unexpectedly, muscle sympathetic nerve activity had no relationship to either total peripheral resistance (r=−0.27; P>0.05) or cardiac output (r=0.23; P>0.05) in women. Our results demonstrate that men and women rely on different integrated physiological mechanisms to maintain a normal arterial pressure despite widely varying sympathetic nerve activity among individuals. These findings may have important implications for understanding how hypertension and other disorders of blood pressure regulation occur in men and women.

Sex and ageing differences in resting arterial pressure regulation: the role of the β-adrenergic receptors

Non‐Technical Summary  In young men, sympathetic nerve activity is directly related to the level of vasoconstrictor tone in the peripheral vasculature. However, in young women this relationship does not exist, suggesting that certain factors (potentially related to the female sex hormones) offset the transfer of sympathetic nerve activity into vasoconstrictor tone in this population. In the present study we show that, in young women, the β‐adrenergic receptors (which cause vasodilatation in response to noradrenaline) blunt the vasoconstrictor effect of resting sympathetic nerve activity in young women. This mechanism does not occur in young men or postmenopausal women. It is possible that the β‐adrenergic receptors may partially protect young women against the sometimes harmful effects of high sympathetic nerve activity. This may explain why the risk of developing hypertension is greater in young men and postmenopausal women (who have very high sympathetic nerve activity) compared to young women.

Complications following 573 Percutaneous Renal Radiofrequency and Cryoablation Procedures

PURPOSE To review complications related to percutaneous renal tumor ablation. MATERIALS AND METHODS Prospectively collected data related to renal radiofrequency (RF) ablation and cryoablation procedures performed from May 2000 through November 2010 were reviewed. This included 573 renal ablation procedures performed in 533 patients to treat 633 tumors. A total of 254 RF ablation and 311 cryoablation procedures were performed; eight patients underwent simultaneous RF ablation and cryoablation. The mean age of patients at the time of the procedure was 70 years (range, 24-93 y), and 382 of 573 procedures (67%) were performed in male patients. Complications were recorded according to the Clavien-Dindo classification scheme. Duration of hospitalization was also documented. RESULTS Of the 573 procedures, 63 produced complications (11.0% overall complication rate). There were 66 reported complications, of which 38 (6.6% of total procedures) were Clavien-Dindo grade II-IV major complications; there were no deaths. Major complication rates did not differ statistically (P = .15) between cryoablation (7.7%; 24 of 311) and RF ablation (4.7%; 12 of 254). Of the complications related to cryoablation, bleeding and hematuria were most common. Bleeding during cryoablation was associated with advanced age, increased tumor size, increased number of cryoprobes, and central position (P < .05). Of those treated with RF ablation, nerve and urothelial injury were most common. Mean hospitalization duration was 1 day for RF ablation and cryoablation. CONCLUSIONS Complications related to percutaneous renal ablation are infrequent. Recognition of potential complications and associated risk factors can allow optimization of periprocedural care.

Nitric oxide contributes to the augmented vasodilatation during hypoxic exercise

We tested the hypotheses that (1) nitric oxide (NO) contributes to augmented skeletal muscle vasodilatation during hypoxic exercise and (2) the combined inhibition of NO production and adenosine receptor activation would attenuate the augmented vasodilatation during hypoxic exercise more than NO inhibition alone. In separate protocols subjects performed forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O2 saturation). In protocol 1 (n= 12), subjects received intra‐arterial administration of saline (control) and the NO synthase inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA). In protocol 2 (n= 10), subjects received intra‐arterial saline (control) and combined l‐NMMA–aminophylline (adenosine receptor antagonist) administration. Forearm vascular conductance (FVC; ml min−1 (100 mmHg)−1) was calculated from forearm blood flow (ml min−1) and blood pressure (mmHg). In protocol 1, the change in FVC (Δ from normoxic baseline) due to hypoxia under resting conditions and during hypoxic exercise was substantially lower with l‐NMMA administration compared to saline (control; P < 0.01). In protocol 2, administration of combined l‐NMMA–aminophylline reduced the ΔFVC due to hypoxic exercise compared to saline (control; P < 0.01). However, the relative reduction in ΔFVC compared to the respective control (saline) conditions was similar between l‐NMMA only (protocol 1) and combined l‐NMMA–aminophylline (protocol 2) at 10% (−17.5 ± 3.7 vs.−21.4 ± 5.2%; P= 0.28) and 20% (−13.4 ± 3.5 vs.−18.8 ± 4.5%; P= 0.18) hypoxic exercise. These findings suggest that NO contributes to the augmented vasodilatation observed during hypoxic exercise independent of adenosine.

Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans

In humans, sympathetic nerve activity (SNA) at rest can vary several‐fold among normotensive individuals with similar blood pressures. We recently showed that a balance exists between SNA and cardiac output, which may contribute to the maintenance of normal blood pressures over the range of resting SNA levels. In the present studies, we assessed whether variability in vascular adrenergic responsiveness has a role in this balance. We tested the hypothesis that forearm vascular responses to noradrenaline (NA) and tyramine (TYR) are related to SNA such that individuals with lower resting SNA have greater adrenergic responsiveness, and vice‐versa. We measured multifibre muscle SNA (MSNA; microneurography), arterial pressure (brachial catheter) and forearm blood flow (plethysmography) in 19 healthy subjects at baseline and during intrabrachial infusions of NA and TYR. Resting MSNA ranged from 6 to 34 bursts min−1, and was inversely related to vasoconstrictor responsiveness to both NA (r= 0.61, P= 0.01) and TYR (r= 0.52, P= 0.02), such that subjects with lower resting MSNA were more responsive to NA and TYR. We conclude that interindividual variability in vascular adrenergic responsiveness contributes to the balance of factors that maintain normal blood pressure in individuals with differing levels of sympathetic neural activity. Further understanding of this balance may have important implications for our understanding of the pathophysiology of hypertension.

Airway management after failure to intubate by direct laryngoscopy: outcomes in a large teaching hospital

PurposeThe purpose of this single-centre database review was to establish the incidence of failure to intubate by direct laryngoscopy, to measure morbidity and mortality associated with this event, and to examine the use and efficacy of alternative airway devices.MethodsDifficult intubation via direct laryngoscopy at Mayo Clinic Rochester is recorded in an electronic database using a functional classification: 0 = no difficulty; 1 = mild to moderate difficulty; and 2 = severe difficulty often requiring a change in intubation technique. Using this database, the total number of intubations was determined for a selected review period and the incidence of failure to intubate by direct laryngoscopy was established. Abstraction of chart data allowed for determination of associated morbidity and mortality, success of alternative airway devices, and case cancellation rate.ResultsDuring the period from August 1, 2001 through December 31, 2002, 37,482 patients underwent general anesthesia with attempted direct laryngoscopy. One hundred sixty-one patients (0.43%) could not be intubated by direct laryngoscopy alone. Morbidity associated with difficult intubation included soft tissue/ dental damage (n = 8), intraoperative cardiac arrest (n = 1), and possible aspiration (n = 1). Three patients required intensive care unit admission. There was no associated mortality. The most commonly used alternative airway device was the flexible fibreoptic scope. Five case cancellations resulted from failure to intubate with alternative devices.ConclusionThe rate of unexpected failure to intubate by direct laryngoscopy is essentially unchanged from earlier studies. While morbidity was low, continued education and early use of alternative difficult airway devices may further limit complications associated with this event.RésuméObjectifÉtablir, par une revue de la base de données d’un seul centre, la fréquence des échecs à intuber par laryngoscopie directe, mesurer la morbidité et la mortalité associées et vérifier l’usage et l’efficacité d’autres instruments d’intubation.MéthodeLes cas d’intubation difficile par laryngoscopie directe à la clinique Mayo de Rochester ont été notés dans une base de données électronique selon une classification fonctionnelle : 0 = aucune difficulté 1 = difficulté légère à modérée et 2 = difficulté sévère exigeant souvent le recours à d’autres techniques d’intubation. Le nombre total d’intubations a été déterminé pour une période de révision choisie et la fréquence des échecs à intuber par laryngoscopie directe a été établie. Un résumé analytique des données a permis de déterminer la morbidité et la mortalité associées, le succès des autres techniques et le taux d’annulation.RésultatsDu premier août 2001 au 31 décembre 2002, 37 482 patients ont eu une anesthésie générale et subi une laryngoscopie directe. Cent soixante et un patients (0,43 %) n’ont pu être intubés par laryngoscopie directe seulement. La morbidité associée à l’intubation difficile comprenait une lésion des tissus mous/des dents (n = 8), un arrêt cardiaque peropératoire (n = 1) et une aspiration possible (n = 1). Trois patients ont dû être admis à l’unité des soins intensifs. Il n’y a pas eu de mortalité associée. L’instrument de remplacement le plus souvent utilisé a été le fibroscope flexible. Cinq annulations ont résulté de l’échec à intuber avec d’autres instruments.ConclusionLe taux imprévu d’échec à intuber par laryngoscopie directe est essentiellement le même depuis les études antérieures. La morbidité est faible, mais une formation continue et un usage précoce d’autres instruments réduiraient davantage les complications qui y sont associées.

Palliation of Painful Metastatic Disease Involving Bone With Imaging-Guided Treatment: Comparison of Patients' Immediate Response to Radiofrequency Ablation and Cryoablation

OBJECTIVE The purpose of this article was to compare periprocedural analgesic requirements and hospital length of stay for treatment of patients with painful metastatic tumors involving bone using either percutaneous radiofrequency ablation (RFA) or cryoablation. MATERIALS AND METHODS A retrospective review was conducted of patients who underwent either imaging-guided cryoablation or imaging-guided RFA for painful metastatic tumors involving bone. The total analgesic usage for 24 hours after the procedure was expressed as a standard morphine-equivalent dose. Analgesic usage at admission served as a baseline for comparison. Total hospital stay was used as an additional measurement of procedure-related morbidity. RESULTS Fifty-eight patients underwent either cryoablation (n = 36) or RFA (n = 22) for painful metastatic tumors involving bone. Twenty-two primary tumors were treated. The most common treatment site was the pelvis (n = 31). There was no significant difference between the two groups with regard to tumor histologic type (p = 0.52) and location (p = 0.72). The median tumor diameter was 4.4 cm for the cryoablation group and 5.0 cm for the RFA group (p = 0.63). Pretreatment pain scores, measured on a scale of 0 to 10, were not significantly different between the two groups: 6.5 for cryoablation and 6.0 for RFA (p = 0.78). Analgesic use in the 24 hours immediately after the procedure decreased significantly by 24 morphine-equivalent doses after cryoablation, whereas it increased by a median of 22 morphine-equivalent doses after RFA (p = 0.03). Total hospital length of stay for patients undergoing cryoablation was a median of 2.5 days less than that for patients receiving RFA (p = 0.003). CONCLUSION The use of cryoablation compared with RFA is associated with a greater reduction in analgesic dose and shorter hospital stays after the procedure in the perioperative time frame.

Age-Related Differences in the Sympathetic-Hemodynamic Balance in Men

As humans age, the tonic level of activity in sympathetic vasoconstrictor nerves increases and may contribute to age-related increases in blood pressure. In previous studies in normotensive young men with varying levels of resting sympathetic nerve activity, we observed a balance among factors contributing to blood pressure regulation, such that higher sympathetic activity was associated with lower cardiac output and lesser vascular responsiveness to &agr;-adrenergic agonists, which limited the impact of high sympathetic activity on blood pressure. In the present study, we tested the hypothesis that older normotensive men would exhibit a similar balance among these variables (sympathetic nerve activity, cardiac output, and &agr;-adrenergic responsiveness) but that this balance would be shifted toward higher sympathetic nerve activity values. We measured muscle sympathetic nerve activity, cardiac output, arterial pressure, and forearm vasoconstrictor responses in 17 older men and compared these with previous data collected in 14 younger men. Muscle sympathetic activity (burst incidence) was positively related to diastolic blood pressure in the older men (r=0.49; P=0.05); this relationship was not observed in young men. In addition, there was no relationship between cardiac output and muscle sympathetic activity (r=0.29; P>0.05) or between muscle sympathetic activity and vasoconstrictor responses in the older men (eg, norepinephrine: r=−0.21; P>0.05). Although our older subjects were normotensive, the relationship between muscle sympathetic nerve activity and diastolic blood pressure and the lack of “balance” among the other variables suggest that these changes with aging may contribute to the risk of sympathetically mediated hypertension in older humans.

Effects of respiratory muscle work on blood flow distribution during exercise in heart failure

Heart failure (HF) patients have a reduced cardiac reserve and increased work of breathing. Increased locomotor muscle blood flow demand may result in competition between respiratory and locomotor vascular beds. We hypothesized that HF patients would demonstrate improved locomotor blood flow with respiratory muscle unloading during activity. Ten patients (ejection fraction = 31 ± 3%) and 10 controls (CTL) underwent two cycling sessions (60% peak work). Session 1 (S1): 5 min of normal breathing (NB), 5 min respiratory muscle unloading with a ventilator, and 5 min of NB. Session 2 (S2): 5 min NB, 5 min of respiratory muscle loading with inspiratory resistance, and 5 min of NB. Measurements included: leg blood flow (LBF, thermodilution), cardiac output , and oesophageal pressure (Ppl, index of pleural pressure). S1: Ppl was reduced in both groups (HF: 73 ± 8%; CTL: 60 ± 13%, P < 0.01). HF: increased (9.6 ± 0.4 vs. 11.3 ± 0.8 l min−1, P < 0.05) and LBF increased (4.8 ± 0.8 vs. 7.3 ± 1.1 l min−1, P < 0.01); CTL: no changes in (14.7 ± 1.0 vs. 14.8 ± 1.6 l min−1) or LBF (10.9 ± 1.8 vs. 10.3 ± 1.7 l min−1). S2: Ppl increased in both groups (HF: 172 ± 16%, CTL: 220 ± 40%, P < 0.01). HF: no change was observed in (10.0 ± 0.4 vs. 10.3 ± 0.8 l min−1) or LBF (5.0 ± 0.6 vs. 4.7 ± 0.5 l min−1); CTL: increased (15.4 ± 1.4 vs. 16.9 ± 1.5 l min−1, P < 0.01) and LBF remained unchanged (10.7 ± 1.5 vs. 10.3 ± 1.8 l min−1). These data suggest HF patients preferentially steal blood flow from locomotor muscles to accommodate the work of breathing during activity. Further, HF patients are unable to vasoconstrict locomotor vascular beds beyond NB when presented with a respiratory load.

Preoperative Gabapentin for Acute Post-thoracotomy Analgesia: A Randomized, Double-Blinded, Active Placebo-Controlled Study

Background:  The role of preoperative gabapentin in postoperative pain management is not clear, particularly in patients receiving regional blockade. Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain. We examined the effect of preoperative gabapentin in thoracotomy patients.