Tasha L. Pike

Anesthesia for Cesarean Delivery and Learning Disabilities in a Population-Based Birth Cohort

Background:Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort. Methods:The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976–1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia). Results:Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia before age 4 yr, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for comparison of CD under regional anesthesia compared to vaginal delivery). Conclusion:Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.

Comparison of two preoperative medical management strategies for laparoscopic resection of pheochromocytoma

OBJECTIVES To compare the intraoperative and postoperative course of patients undergoing laparoscopic pheochromocytoma resection at 2 institutions (Mayo Clinic and Cleveland Clinic) with differing approaches to preoperative preparation. Patients undergoing adrenalectomy for pheochromocytoma typically undergo a preoperative preparation to normalize their blood pressure and intravascular volume. However, no consensus has been reached regarding the best preoperative preparation regimen. METHODS A retrospective chart review was performed of 50 Mayo Clinic patients and 37 Cleveland Clinic patients who had undergone laparoscopic pheochromocytoma resection. Mayo Clinic predominantly used the long-lasting nonselective alpha(1,2) antagonist phenoxybenzamine, and Cleveland Clinic predominately used selective alpha(1) blockade. Data regarding the intraoperative hemodynamics and postoperative complications were collected. RESULTS Almost all patients at Mayo Clinic received phenoxybenzamine (98%). At Cleveland Clinic, the predominant treatment (65%) was selective alpha(1) blockade (doxazosin, terazosin, or prazosin). Intraoperatively, patients at Cleveland Clinic had a greater maximal systolic blood pressure (209 +/- 44 mm Hg versus 187 +/- 30 mm Hg, P = .011) and had received a greater amount of intravenous crystalloid (median 5000, interquartile range 3400-6400, versus median 2977, interquartile range 2000-3139; P <.010) and colloid (median 1000, interquartile range 500-1000, versus median 0, interquartile range 0-0; P <.001). At Mayo Clinic, more patients had received phenylephrine (56.0% versus 27.0%, P = .009). No differences were found in the postoperative surgical outcomes, and the hospital stay was comparable between the 2 groups. CONCLUSIONS Differences in the preoperative preparation and intraoperative management were associated with differences in intraoperative hemodynamics but not with clinically significant outcomes in patients undergoing laparoscopic adrenalectomy for pheochromocytoma at 2 large tertiary care centers.

Exercise intensity-dependent contribution of β-adrenergic receptor-mediated vasodilatation in hypoxic humans

We previously reported that hypoxia‐mediated reductions in α‐adrenoceptor sensitivity do not explain the augmented vasodilatation during hypoxic exercise, suggesting an enhanced vasodilator signal. We hypothesized that β‐adrenoceptor activation contributes to augmented hypoxic exercise vasodilatation. Fourteen subjects (age: 29 ± 2 years) breathed hypoxic gas to titrate arterial O2 saturation (pulse oximetry) to 80%, while remaining normocapnic via a rebreath system. Brachial artery and antecubital vein catheters were placed in the exercising arm. Under normoxic and hypoxic conditions, baseline and incremental forearm exercise (10% and 20% of maximum) was performed during control (saline), α‐adrenoceptor inhibition (phentolamine), and combined α‐ and β‐adrenoceptor inhibition (phentolomine/propranolol). Forearm blood flow (FBF), heart rate, blood pressure, minute ventilation, and end‐tidal CO2 were determined. Hypoxia increased heart rate (P < 0.05) and minute ventilation (P < 0.05) at rest and exercise under all drug infusions, whereas mean arterial pressure was unchanged. Arterial adrenaline (P < 0.05) and venous noradrenaline (P < 0.05) were higher with hypoxia during all drug infusions. The change (Δ) in FBF during 10% hypoxic exercise was greater with phentolamine (Δ306 ± 43 ml min−1) vs. saline (Δ169 ± 30 ml min−1) or combined phentolamine/propranolol (Δ213 ± 25 ml min−1; P < 0.05 for both). During 20% hypoxic exercise, ΔFBF was greater with phentalomine (Δ466 ± 57 ml min−1; P < 0.05) vs. saline (Δ346 ± 40 ml min−1) but was similar to combined phentolamine/propranolol (Δ450 ± 43 ml min−1). Thus, in the absence of overlying vasoconstriction, the contribution of β‐adrenergic mechanisms to the augmented hypoxic vasodilatation is dependent on exercise intensity.

Adenosine receptor antagonist and augmented vasodilation during hypoxic exercise

We tested the hypothesis that adenosine contributes to augmented skeletal muscle vasodilation during hypoxic exercise. In separate protocols, subjects performed incremental rhythmic forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O2 saturation). In protocol 1 (n = 8), subjects received an intra-arterial administration of saline (control) and aminophylline (adenosine receptor antagonist). In protocol 2 (n = 10), subjects received intra-arterial phentolamine (alpha-adrenoceptor antagonist) and combined phentolamine and aminophylline administration. Forearm vascular conductance (FVC; in ml x min(-1).100 mmHg(-1)) was calculated from forearm blood flow (in ml/min) and blood pressure (in mmHg). In protocol 1, the change in FVC (DeltaFVC; change from normoxic baseline) during hypoxic exercise with saline was 172 +/- 29 and 314 +/- 34 ml x min(-1) x 100 mmHg(-1) (10% and 20%, respectively). Aminophylline administration did not affect DeltaFVC during hypoxic exercise at 10% (190 +/- 29 ml x min(-1)x100 mmHg(-1), P = 0.4) or 20% (287 +/- 48 ml x min(-1) x 100 mmHg(-1), P = 0.3). In protocol 2, DeltaFVC due to hypoxic exercise with phentolamine infusion was 313 +/- 30 and 453 +/- 41 ml x min(-1) x 100 mmHg(-1) (10% and 20% respectively). DeltaFVC was similar at 10% (352 +/- 39 ml min(-1) x 100 mmHg(-1), P = 0.8) and 20% (528 +/- 45 ml x min(-1) x 100 mmHg(-1), P = 0.2) hypoxic exercise with combined phentolamine and aminophylline. In contrast, DeltaFVC to exogenous adenosine was reduced by aminophylline administration in both protocols (P < 0.05 for both). These observations suggest that adenosine receptor activation is not obligatory for the augmented hyperemia during hypoxic exercise in humans.

Dietary sodium restriction and β2‐adrenergic receptor polymorphism modulate cardiovascular function in humans

Dietary Na+ intake influences β2‐adrenergic receptor (β2AR) responsiveness. While receiving a normal Na+ diet (150 mmol day−1), subjects homozygous for glycine at amino acid 16 (Gly16) have greater forearm β2AR‐mediated vasodilatation than subjects homozygous for arginine (Arg16), an effect that is mediated by endothelial NO. We tested the hypothesis that dietary Na+ restriction eliminates genotype differences in forearm and systemic β2AR‐mediated dilatation in these groups. We measured heart rate, mean arterial pressure and cardiac output (CO, acetylene breathing) responses to administration of intravenous terbutaline (TRB) before and after 5 days of low dietary Na+ intake (10 mmol day−1) in healthy Gly16 (n= 17; age, 31 ± 7 year) and Arg16 homozygotes (n= 15; age, 29 ± 8 year). After the low‐Na+ diet, a catheter was placed in the brachial artery to measure forearm blood flow (FBF, plethysmography) responses to administration of isoprenaline (isoproterenol) before and after NO inhibition with NG‐mono‐methyl‐l‐arginine (l‐NMMA). In the Gly16 group, the low‐Na+ diet decreased baseline CO from 6.4 ± 1.4 to 5.5 ± 1.2 l min−1 (P= 0.003, paired t test), tended to decrease stroke volume from 97.0 ± 20.6 to 86.9 ± 21.7 ml (P= 0.06) and increased peripheral resistance from 1106 ± 246 to 1246 ± 222 dynes s cm−5 (P= 0.02); significant effects of the low‐Na+ diet were not observed in Arg16 subjects. In a repeated measures ANOVA, the responses of all cardiovascular measures to systemic administration of TRB were not influenced by genotype or diet. Additionally, the FBF response to incremenetal doses of isoprenaline did not differ between genotype groups before or after administration of l‐NMMA. We conclude that dietary Na+ restriction blunted the increased forearm NO‐mediated β2AR responsiveness in Gly16 homozygotes observed in a previous study after normal dietary Na+ intake, while baseline CO decreased and peripheral resistance increased in this group. This study provides evidence that dietary Na+ modulates effects of the Arg16Gly polymorphism on cardiovascular function.

A comparison of peripheral skin blood flow and temperature during endoscopic thoracic sympathotomy

The assessment of sympathetic denervation to the upper extremities during surgery for hyperhidrosis is essential in predicting postoperative outcome, particularly for endoscopic thoracic chain sympathotomy, a recently described, minimally destructive technique that minimizes postoperative compensatory hyperhidrosis. To test the hypothesis that skin blood flow (SkBF; laser Doppler flowmetry) provides a faster and more reliable indication of denervation than temperature (temp), we prospectively compared palmar SkBF and fingertip temp in 10 patients undergoing endoscopic thoracic chain sympathotomy for essential hyperhidrosis. From baseline to peak values, palmar SkBF (mean ± sem) increased 273.3 ± 24.7 arbitrary units and 252.4 ± 30.1 arbitrary units, whereas temp increased 0.9°C ± 0.3°C and 1.5°C ± 0.6°C on the right and left, respectively. Upon effective sympathotomy of the right thoracic chain, the time to peak SkBF was 43 ± 13 s, whereas the time to peak temp was 277 ± 53 s (P < 0.001). On the left, the time to peak SkBF was 81 ± 14 s, and time to peak temp was 305 ± 34 s (P < 0.001). All patients considered the sympathotomy successful. We conclude that laser Doppler SkBF is superior to temp in temporal resolution for assessment of denervation during sympathotomy and that it provides a superior qualitative and quantitative adjunct to monitoring denervation.

Ambulatory arterial stiffness index is not correlated with the pressor response to laboratory stressors in normotensive humans

Background Ambulatory arterial stiffness index (AASI) is a novel estimate of arterial stiffness, which independently predicts cardiovascular mortality, even in normotensive individuals. Additionally, other markers derived from ambulatory blood pressure (BP) monitoring, including variability, pulse pressure, nocturnal dipping, and morning BP surge, have all been shown to be predictive of end-organ damage and cardiovascular disease. Exaggerated cardiovascular reactivity to sympathoexcitatory stimuli may also predict future incidence of hypertension. The purpose of this investigation was to test the hypothesis that AASI and other derivations of ambulatory BP, including pulse pressure, 24-h blood pressure variability, dipping, and morning surge, would be correlated with the pressor response to common physiological stress maneuvers. Method We measured continuous heart rate and arterial BP during head-up tilt, mental stress, cold pressor test, and isometric handgrip to fatigue in 67 healthy, normotensive, nonobese individuals (43 women, 24 men, mean age ± SD: 28 ± 6 years). Then, 24-h ambulatory BP was obtained, and AASI was defined as 1 minus the slope of diastolic on systolic BP in individual 24-h ambulatory BP recordings. Results Although all measures were widely variable among patients, there was no relationship between AASI, pulse pressure, blood pressure variability, dipping, and morning surge with the pressor responses. Conclusion We conclude that in the absence of aging, cardiovascular, or autonomic disease, the novel stiffness index (AASI) or other ambulatory BP indices are either poorly correlated with or mechanistically unrelated to the complex pressor response to common provocations of sympathoexcitation.

12 CARDIOVASCULAR MODULATION OF DIETARY SODIUM RESTRICTION AND b2-ADRENERGIC RECEPTOR POLYMORPHISM IN HUMANS.

Dietary sodium intake has been shown to influence b2-adrenergic receptor (b2-AR) responsiveness, and the Gly allele of the Arg16/Gly b2-AR polymorphism has been associated with hypertension in a linkage analysis in Rochester, MN. We have also shown that Gly homozygotes (GG) have greater forearm b2-AR mediated vasodilation than Arg (AA) after a controlled Na+ diet (150 mmol - day-1), and the difference is mediated by endothelial NO. The purpose of this study was to test the hypothesis that dietary Na+ restriction affects forearm and systemic b2-mediated dilation in healthy normotensive humans GG (n = 17) vs AA (n = 15). We measured HR, MAP, and CO (acetylene breathing) responses to intravenous infusion of terbutaline (TRB) before and after 5 days of dietary Na+ restriction (10 mmol - day-1). Also following the diet, a brachial artery catheter was placed to measure forearm blood flow (FBF, plethysmography) responses to isoproterenol (ISO) before and after NO inhibition with L-NMMA. There was a main effect of diet (p < .03) on weight loss, increased urine volume, and 24-hour urinary excretion of Na+ but no influence from genotype. Diet significantly decreased baseline CO in GG (pre- vs postdiet mean ± SD: 6.4 ± 1.4 to 5.5 ± 1.2 L - min-1; p = .003) but not in AA (5.8 ± 1.3 to 5.6 ± 1.0 L - min-1, NS) and increased peripheral resistance in GG (p = .02) but not AA. Baseline HR, MAP, and stroke volume were similar between groups, and the responses of all cardiovascular measures to TRB were not influenced by genotype or diet. In contrast to previous findings after a normal Na+ diet, the FBF dose response curves to ISO were not different based on genotype (p = .51). L-NMMA decreased baseline FBF and significantly blunted the response to ISO, but there was no evidence to suggest that the responses were influenced by genotype (p = .89, genotype-by-ISO-by-L-NMMA interaction). We conclude that dietary Na+ restriction negates the increased forearm NO-mediated, b2-AR responsiveness in GG subjects, which may explain the diet-evoked baseline increase in peripheral resistance and decrease in CO in this group, providing evidence that Na+ intake modulates cardiovascular indices based on the Arg16/Gly b2-AR polymorphism. Supported by GCRC RR-00585, NCRR K23-1752, HL 63328.