Changes in the catecholamine plasma level 3 months after aortocoronary bypass operation

Plasma catecholamine levels were obtained during diagnostic heart catheterization from the pulmonary artery and aorta and, similarly, renin levels were determined in the pulmonary artery in 31 patients with coronary heart disease and 18 normal controls. 3 months after aorto-coronary bypass surgery the patients with coronary heart disease underwent repeat heart catheterization and the epinephrine, norepinephrine and renin levels were compared with those obtained before operation. Norepinephrine decreased in the aorta from (means +/- SEM) 475 +/- 57 pg/ml to 360 +/- 38 pg/ml (p less than 0.001) postoperatively (controls 225 +/- 21 pg/ml). Epinephrine decreased from 121 +/- 11 pg/ml to 108 +/- 16 pg/ml (p less than 0.001) postoperatively (controls 84 +/- 9 pg/ml). This shows that postoperative relief from myocardial ischemia is associated with normalization of the preoperatively elevated plasma catecholamine levels).     

Cardiovascular and endocrine responses during the cold pressor test in subjects with cervical spinal cord injuries

OBJECTIVE: To investigate cardiovascular regulation and endocrine responses during the cold pressor test in patients with chronic spinal cord injury (SCI). DESIGN: Experimental and control study. SETTING: University laboratory, department of rehabilitation medicine, in Japan. PARTICIPANTS: Eight quadriplegic subjects with complete spinal cord transection at the C6 to C8 level and 6 age-matched healthy subjects. INTERVENTIONS: Cardiovascular and endocrine responses were examined during 2 minutes of control, 3 minutes of ice-water immersion of the foot, followed by a 3-minute recovery. MAIN OUTCOME MEASURES: Blood pressure, heart rate, the Borg 15-point Rating of Perceived Pain Scale, and blood samples for measurement of plasma norepinephrine, epinephrine, plasma renin activity, plasma aldosterone, and arginine vasopressin. RESULTS: The rise in the mean arterial blood pressure during the cold pressor test in patients with SCI (baseline, 81.6+/-3.7mmHg; increased by 30%+/-6.1%) was significantly (P<.05) higher than that in healthy subjects (baseline, 101.2+/-4.5mmHg; increased by 20%+/-4.5%). The SCI subjects had no change in heart rate throughout the test, in contrast to the tachycardia noted in normal subjects. Baseline plasma norepinephrine in SCI subjects (63.0+/-18.3pg/mL) was significantly lower than in normal subjects (162.3+/-19.6pg/mL) and plasma norepinephrine increased significantly during the cold pressor test in both groups. CONCLUSIONS: In the SCI subjects, a reflex sympathetic discharge through the isolated spinal cord results in a more profound rise in mean blood pressure during ice-water immersion. This response was free of inhibitory impulses from supraspinal center and baroreceptor reflexes, either of which might restrain the increase in blood pressure.     

Pharmacologic reduction of sympathetic drive increases platelet alpha-2-receptor number

Several lines of evidence implicate sympathetic nervous system involvement in the pathophysiology of essential hypertension in man. Extrapolations are frequently made from in vitro measurements of plasma catecholamine levels to the physiologic role of the sympathetic system in hypertension. We assessed the utility and validity of such extrapolation from in vitro to in vivo measures of adrenergic function. Addition of guanadrel to diuretic therapy in 11 patients with essential hypertension reduced supine intra-arterial blood pressure from 135 +/- 14/76 +/- 9 to 127 +/- 13/67 +/- 5 mm Hg (P less than 0.02). Supine heart rate was also reduced, from 77 +/- 14 to 63 +/- 13 bpm (P less than 0.001). Plasma norepinephrine levels fell from 303 +/- 107 to 170 +/- 46 pg/ml (P less than 0.01). Platelet alpha 2-receptor number ([3H]yohimbine maximal binding) increased from 204 +/- 77 to 301 +/- 150 fmol/mg (P less than 0.02). The pupillary mydriatic response to phenylephrine and the forearm arterial vasoconstrictor response to intra-arterial norepinephrine did not change. Thus guanadrel reduced blood pressure by decreasing sympathetic tone. In this milieu of low sympathetic activity the platelet alpha 2-receptor number increased, but physiologic responses to exogenous alpha-agonists did not change. Caution is therefore advised when extrapolating from in vitro measurement of plasma catecholamine levels and platelet alpha 2-receptor number to the in vivo physiologic significance.     

What stimulates atrial natriuretic factor release during exercise?

Prior studies have shown that circulating atrial natriuretic factor (ANF) increases during short-term exercise, but the mechanism controlling ANF release, as well as the effect of exercise training on ANF release, remains unclear. Fifteen healthy mongrel dogs underwent short-term exercise testing before and after a 12-week period of exercise training (n = 8) or cage confinement (n = 7). ANF, norepinephrine, epinephrine, right atrial pressure, and heart rate were measured simultaneously at rest and during exercise at the time of each acute exercise study. Data were analyzed for all animals with normal baseline ANF values. Exercise training had no modulating effect on circulating ANF levels at rest or during exercise. Therefore, data before and after exercise training or cage confinement were grouped (n = 24) to determine the effects of short-term exercise. ANF levels increased from 49 +/- 2 pg/ml at rest to 60 +/- 4 pg/ml during exercise (p less than 0.05). Heart rate, norepinephrine, and epinephrine values also increased, but right atrial pressure actually decreased from 2.3 +/- 0.9 mm Hg at rest to -3.8 +/- 0.9 mm Hg during exercise (p less than 0.05). There was no correlation between ANF concentrations and levels of these other variables either at rest of during exercise. By demonstrating an increase in ANF with a simultaneous decrease in right atrial pressure, this study clearly shows that increased right atrial pressure is not the secretory stimulus for ANF release during exercise in the normal dog. The lack of correlation between ANF and right atrial pressure, heart rate, norepinephrine, and epinephrine levels suggests that factors other than these variables stimulate ANF release during short-term exercise.     

Cardiovascular effects of verapamil in essential hypertension

Calcium antagonists may affect the regulation of body sodium and adrenergic-dependent mechanisms. Exchangeable sodium, blood volume, plasma norepinephrine, renin, aldosterone, pressor responsiveness to norepinephrine, heart rate responses to isoproterenol, and lipid metabolism were studied in 15 patients with essential hypertension after 8 weeks of treatment with verapamil (348 +/- 68 (SD) mg/day). Supine blood pressure decreased from 153/103 +/- 19/12 mm Hg to 140/95 +/- 14/12 mm Hg (P less than 0.01). Exchangeable sodium, blood volume, plasma norepinephrine, renin and aldosterone, serum total cholesterol, the lipoprotein fractions, and apoprotein levels were unchanged. The norepinephrine pressor and the isoproterenol chronotropic doses tended to increase, whereas the dose-response curve of blood pressure related to plasma norepinephrine was significantly displaced to the right (F = 5.34; P less than 0.05). The antihypertensive effect of verapamil is associated with a decreased cardiovascular pressor responsiveness to norepinephrine without changes in endogenous noradrenergic activity. Moreover, verapamil does not modify the sodium/fluid volume state, the activity of the renin-angiotensin aldosterone axis, or lipid metabolism.     

Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension

Recent experimental studies showed that inhibition of angiotensin II synthesis may reduce sympathetic activity as evaluated by plasma catecholamine assay, sharing in the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. Fifteen patients with essential hypertension were studied. Blood pressure and heart rate were evaluated both at rest and after stressor laboratory tests, before and four hours after administration of 20 mg of enalapril maleate and on the 14th and 120th days of continued administration. At the same time, blood samples were drawn for determinations of plasma renin activity, ACE, angiotensin II, plasma aldosterone concentration, and plasma norepinephrine levels. Enalapril in a dosage of 20 mg/day significantly and progressively lowered systolic and diastolic blood pressure at rest, with maximal decreases observed on the 120th day of the study period (P less than 0.001). Heart rate at rest and after exercise showed no significant differences throughout the study period. Good blood pressure control was observed during stressor laboratory tests. The greatest impact of blood pressure was observed on the 120th day during dynamic exercise (mean blood pressure from 139 +/- 3.9 to 111.5 +/- 6.3 mmHg; P less than 0.01) and on the 14th day during the cold pressure test (mean blood pressure from 133.3 +/- 3.9 to 111.2 +/- 4.7 mmHg; P less than 0.005). A marked and persistent ACE inhibition and a gradual and progressive decrease of angiotensin II (from 12.42 +/- 2.15 to 5.45 +/- 1.68 pg/ml; P less than 0.005) characterized the humoral activity of enalapril maleate. Moreover, a significant decrease of plasma norepinephrine levels was observed during the follow-up period with maximal reduction on the 120th day (from 311 +/- 34 to 197 +/- 33 pg/ml; P less than 0.01). It has been demonstrated that the pressor effect of angiotensin II was blunted during exercise. Our hemodynamic and humoral results appear to confirm the hypothesis that enalapril maleate may reduce blood pressure by direct inhibition of ACE and of kininase II as well as by a decreased sympathetic output, which may be secondary to angiotensin II inhibition. These results agree with the recent experimental demonstration of a reduced sympathetic nervous response to nerve stimulation during ACE inhibition.     

Animal-assisted therapy in patients hospitalized with heart failure.

BACKGROUND: Animal-assisted therapy improves physiological and psychosocial variables in healthy and hypertensive patients. OBJECTIVES: To determine whether a 12-minute hospital visit with a therapy dog improves hemodynamic measures, lowers neurohormone levels, and decreases state anxiety in patients with advanced heart failure. METHODS: A 3-group randomized repeated-measures experimental design was used in 76 adults. Longitudinal analysis was used to model differences among the 3 groups at 3 times. One group received a 12-minute visit from a volunteer with a therapy dog; another group, a 12-minute visit from a volunteer; and the control group, usual care. Data were collected at baseline, at 8 minutes, and at 16 minutes. RESULTS: Compared with controls, the volunteer-dog group had significantly greater decreases in systolic pulmonary artery pressure during (-4.32 mm Hg, P = .03) and after (-5.78 mm Hg, P = .001) and in pulmonary capillary wedge pressure during (-2.74 mm Hg, P = .01) and after (-4.31 mm Hg, P = .001) the intervention. Compared with the volunteer-only group, the volunteer-dog group had significantly greater decreases in epinephrine levels during (-15.86 pg/mL, P = .04) and after (-17.54 pg/mL, P = .04) and in norepinephrine levels during (-232.36 pg/mL, P = .02) and after (-240.14 pg/mL, P = .02) the intervention. After the intervention, the volunteer-dog group had the greatest decrease from baseline in state anxiety sum score compared with the volunteer-only (-6.65 units, P =.002) and the control groups (-9.13 units, P < .001). CONCLUSIONS: Animal-assisted therapy improves cardiopulmonary pressures, neurohormone levels, and anxiety in patients hospitalized with heart failure.     

Comparison of sympathetic modulation induced by single oral doses of mibefradil, amlodipine, and nifedipine in healthy volunteers

OBJECTIVE: Our objective was to compare the sympathetic modulation induced by oral administration of a single dose of 20 mg of standard nifedipine, of 10 mg of amlodipine, and of 100 mg of mibefradil. METHODS: Sixteen healthy male volunteers participated in this double-blind, randomized, placebo-controlled, crossover four-period study. The sympathetic modulation induced by treatments was evaluated during 24 hours after drug administration by neurohormonal dosages, hemodynamic parameter measurements, and spectral analysis of heart rate and blood pressure. RESULTS: We observed a significant (P <.05) decrease in diastolic blood pressure 1 hour after the administration of nifedipine (62 +/- 9 to 59 +/- 5 mm Hg) with concomitant increases in heart rate (59 +/- 5 to 74 +/- 8 bpm) and neurohormones (53 +/- 18 to 83 +/- 50 pg/mL for aldosterone, 157 +/- 56 to 282 +/- 119 pg/mL for norepinephrine, and 9.8 +/- 5.5 to 40.2 +/- 97.1 pg/mL for active renin). No significant modification of these parameters was observed with amlodipine and mibefradil, except an isolated increase of norepinephrine plasma level 2 hours after the administration of mibefradil (133.1 +/- 67.1 to 210.9 +/- 92.5 pg/mL). The spectral analysis over 24 hours of Mayer waves of systolic blood pressure did not show any significant change over time in the different groups. When the analysis was performed during the first 4 hours after treatment administration, we observed a decrease of Mayer waves of systolic blood pressure with nifedipine (2.21 +/- 1.45 mm Hg(2) versus 3.53 +/- 1.85 mm Hg(2) with placebo). These results indicate that oral single doses of mibefradil and amlodipine do not induce baroreflex-mediated clinical changes in healthy volunteers. The single oral dose of nifedipine resulted in a marked increase in sympathetic tone and a decrease in systolic blood pressure variability early after oral administration. CONCLUSION: Mibefradil, the nondihydropyridine calcium antagonist, exerts much less sympathetic stimulation than nifedipine.     

The Plasma Catecholamine Responses to Ventricular Pacing: Implications for Rate Responsive Pacing

Many patients with WI and WIR pacemakers will alternate between periods of sinus rhythm and ventricular pacing. These rhythm shifts may be poorly tolerated by some patients. Changes in plasma Catecholamine levels during these rhythm shifts may contribute to these patients'symptoms. We measured blood pressure, ejection fraction and plasma norepinephrine, epinephrine, and dopamine serially in nine patients with normal left ventricular ejection fractions and WI pacemakers during sinus rhythm and at paced rates of 10 beats per minute (bpm) above sinus rates (10 + NSR), 100 bpm, and 130 bpm. The mean norepinephrine level at baseline was 143 ± 16 pg/mL and increased to 166 ± 36 pg/mL at 10 + NSR, 204 ± 47 pg/mL at 100 bpm, and 182 ± 34 pg/mL at 130 bpm. These increases corresponded to mean percent changes from baseline of 17% (P = 0.02), 33% (P = 0.002), and 24% (P = 0.07), respectively. The magnitude of the norepinephrine response was not correlated with the pacing rate. The mean plasma epinephrine level at baseline was 57 ± 6 pg/mL and peaked at 51 ± 12 pg/mL at 10 + NSR, 89 ± 31 pg/mL at 100 bpm and 101 ± 28 pg/mL at 130 bpm. These increases corresponded to mean percent changes from baseline of- 10% (P = NS), 30% (P = 0.07), and 89% (P = 0.02), respectively. No trends in the dopamine response to pacing were noted. During ventricular pacing there were no significant changes in mean blood pressure and only slight changes in ejection fraction. The individual percent changes in plasma norepinephrine and epinephrine at 100 bpm were inversely correlated to the changes in systolic blood pressure (R =−0.68, P = 0.06, and R =−0.81, P = 0.03, respectively). These results suggest that plasma norepinephrine and epinephrine increase acutely in response to ventricular pacing at rates commonly seen during rate responsive ventricular pacing.     

Abnormal cardiovascular response to exercise in patients with peripheral arterial disease: Implications for management

Exercise is beneficial in improving claudication and functional capacity in patients with peripheral arterial disease (PAD). However, the physiologic response during and after exercise testing in this patient population has not been fully described. This study examined the cardiovascular response to exercise and explored the potential contribution of vascular noncompliance to exercise-induced hypertension in 124 patients with PAD and claudication and 31 comparison (C) patients with PAD with no walking limitations. Maximal walking distance was determined by an exercise treadmill test. Heart rate and blood pressure were monitored before, during, and immediately after an exercise test. Vascular compliance of the small and large vessels was measured using pulse waveform analysis. Individuals with low supine resting heart rate had longer pain-free walking distance (r = -0.195, P = .019) and maximal walking versus the C group (62 beats/min, standard deviation [SD] = 10, P = .02). Systolic blood pressure during supine rest was significantly lower for the PAD group (mean = 141 mm Hg, +/- SD = 22) versus the C group (mean = 153 mm Hg, +/- SD = 20, P = .003). Vascular compliance of large vessels was higher in the C group (mean = 4.13 +/- 4.13 mL/mm Hg x 100) compared with the PAD group (mean = 2.95 +/- 1.6 mL/mm Hg x 100). This study describes the exaggerated exercise cardiovascular response and impaired vascular compliance in patients with PAD. These results provide further evidence supporting the importance of a monitored treadmill exercise test before initiation of an exercise program to ensure safe and accurate exercise recommendations, and to identify individuals that require more intensive pharmacotherapy to prevent exercise-induced hypertension and tachycardia.     

Sequential changes in atrial pressures, dimensions, and plasma atrial natriuretic factor concentrations during volume loading in hemodynamically normal human subjects.

The effects of volume loading on atrial pressures and dimensions, plasma levels of atrial natriuretic factor (ANF), and other neurohormonal variables were studied in 11 patients with normal hemodynamics with the patients in a supine -15 degree left decubitus posture by infusing 750 ml of normal saline solution over 30 minutes. Right and left atrial areas were measured by two-dimensional echocardiography. Plasma ANF level was sampled simultaneously from the pulmonary artery, aorta, and femoral artery and vein. At 30 minutes into the infusion, pulmonary capillary wedge pressure and right atrial pressure increased from 5.6 +/- 2.8 mm Hg (mean +/- SD) and 6.4 +/- 2.2 mm Hg to 10.2 +/- 3.2 and 9.5 +/- 2.2 mm Hg, respectively (both p less than 0.01). Left atrial area increased from 12.6 +/- 2.2 cm2 to 15.0 +/- 2.1 cm2 (p less than 0.05), whereas right atrial area did not change. Plasma ANF levels from all sampling sites increased significantly (e.g., 43 +/- 21 pg/ml to 71 +/- 62 pg/ml in the femoral artery, p less than 0.05). Plasma norepinephrine and renin levels were unchanged, whereas aldosterone level declined significantly. At 30 minutes after termination of the infusion, atrial pressures declined to baseline values in all patients. However, left atrial area remained significantly increased, and a trend for systemic arterial plasma ANF level to remain increased was seen. Plasma aldosterone level remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of intravenous dilevalol with placebo in moderate hypertension

Dilevalol, an agent that combines nonselective beta-blocking and beta 2-mediated vasodilating properties, was compared with placebo in 16 subjects with moderate hypertension in a double-blind crossover study. Dilevalol or a placebo was administered intravenously in bolus injections of 25, 50, and 50 mg at 15-minute intervals. Fifteen minutes after a cumulative dose of 125 mg, the blood pressure was lowered by 11/9 mm Hg, compared with 2/1 mm Hg after placebo (p less than 0.01 between groups for systolic and diastolic blood pressure), an effect that persisted for at least 105 minutes. Standing systolic blood pressure was also lowered in dilevalol-treated patients without orthostatic symptoms. No significant effects on heart rate were noted. Fifteen minutes after the last dose of dilevalol, plasma norepinephrine levels increased from a baseline of 200 +/- 24 to 495 +/- 44 pg/ml (p less than 0.01), compared with a nonsignificant rise from 262 +/- 21 to 306 +/- 28 pg/ml with placebo vehicle. Dilevalol also increased alpha-human atrial natriuretic factor by 5.4 pg/ml, compared with 0.5 pg/ml after placebo (p less than 0.01 between groups). Plasma renin activity and plasma epinephrine, aldosterone, and cyclic guanosine monophosphate levels were unchanged by dilevalol. There were no significant adverse effects with dilevalol administration. Compared with placebo, dilevalol given intravenously appears to be safe and effective antihypertensive treatment.     

Cerebral response to norepinephrine compared with fluid resuscitation in ovine traumatic brain injury and systemic inflammation

OBJECTIVE: Traumatic brain injury is frequently accompanied by a systemic inflammatory response. Systemic inflammation was associated with cerebral hyperperfusion uncoupled to global oxygen metabolism in ovine head trauma. The present study investigated the cerebral effects of cerebral perfusion pressure (CPP) management performed by either fluid resuscitation or vasopressor treatment of low CPP induced by systemic inflammation. DESIGN: Nonrandomized experimental study. SETTING: University hospital laboratory. SUBJECTS: A total of 12 adult sheep. INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: Sheep were anesthetized and ventilated throughout the experimental period (13 hrs). After baseline measurements (hour 0), blunt head trauma was induced by a nonpenetrating stunner. After postinjury measurements (hour 2), all animals received continuous endotoxin infusion. At hour 10, one group (n = 6) was infused with hydroxyethyl starch until CPP reached 60-70 mm Hg. A second group (n = 6) received norepinephrine for CPP elevation. In the norepinephrine group, blood was isovolemically exchanged by hydroxyethyl starch to achieve comparable hematocrit levels. Head trauma increased intracranial pressure and decreased brain tissue oxygen tension. Endotoxemia induced a hyperdynamic cardiovascular response with increased internal carotid blood flow in the presence of systemic hypotension and decreased CPP. Hydroxyethyl starch infusion further increased internal carotid blood flow from (mean +/- sd) 247 +/- 26 (hour 10) to 342 +/- 42 mL/min (hour 13) and intracranial pressure from 20 +/- 4 (hour 10) to a maximum of 25 +/- 3 mm Hg (hour 12) but did not significantly affect brain tissue oxygen tension, sinus venous oxygen saturation and oxygen extraction fraction. Norepinephrine increased internal carotid blood flow from 268 +/- 19 to 342 +/- 58 mL/min and intracranial pressure from 22 +/- 11 to 24 +/- 11 mm Hg (hour 10 vs. hour 13) but significantly increased sinus venous oxygen saturation from 49 +/- 4 (hour 10) to a maximum of 59 +/- 6 mm Hg (hour 12) and decreased oxygen extraction fraction. The increase in brain tissue oxygen tension during norepinephrine treatment was not significant. CONCLUSION: We conclude that despite identical carotid blood flows, only CPP management with norepinephrine reduced the cerebral oxygen deficit in this model.     

Paradoxical changes in brain natriuretic peptide levels and loading conditions after intravenous conscious sedation.

BACKGROUND: Elevated filling pressure and wall stress have been proposed as stimuli for elevated brain natriuretic peptide (BNP) levels. Narcotic and benzodiazepine sedation, such as is used for transesophageal echocardiography (TEE), is known to decrease filling pressures. We hypothesized that lower filling pressure and wall stress associated with intravenous conscious sedation (IVCS) would lead to lower BNP levels. METHODS: We studied BNP levels, blood pressure, and echocardiographic indices of filling pressure and wall stress before and after IVCS and TEE. RESULTS: When data before and after IVCS and TEE were compared, mean blood pressure decreased (149 +/- 24/83 +/- 14 mm Hg vs 126 +/- 29/69 +/- 14; P < .01), as did mitral Doppler E wave velocity (82 +/- 23 cm/s vs 76 +/- 22; P < .05), right ventricular/atrial gradient (31 +/- 10 mm Hg vs 29 +/- 13; P < .05), and wall stress. However, BNP levels increased (195 +/- 407 pg/mL vs 238 +/- 458; P < .01). CONCLUSIONS: In a series of patients undergoing clinically indicated TEE, BNP levels increase above baseline after IVCS. The increase in BNP occurs despite lower blood pressure, lower mitral Doppler E velocity, lower right ventricular/atrial gradient, and lower wall stress compared with baseline. The mechanism of the paradoxical increase in BNP is not entirely clear, but it may conceivably be a result of counterregulatory hormone release caused by acute decrease in blood pressure.     

Plasma Aldosterone Concentration at Delivery and during the Newborn Period

Aldosterone concentrations in plasma of women on normal sodium intake undergoing cesarean section were 3.7+/-1.4 ng/100 ml (mean+/-1 SD). These values were significantly lower (P < 0.001) than those observed in mothers on normal sodium diet, delivered by the vaginal route (14.9+/-7.0 ng/100 ml). A significant elevation (P < 0.001) of the concentrations was found if the mothers had been on sodium restriction and/or diuretics (44.9+/-24.2 ng/100 ml). In supine position, adult nonpregnant subjects have aldosterone concentrations in plasma of 1.7+/-1.4 ng/100 ml on normal sodium intake and of 16.7+/-8.1 ng/100 ml on low sodium diet.Simultaneous determinations of aldosterone levels in cord blood showed that cord values were significantly higher than those of the corresponding mother (P < 0.01 by paired t test). However, values in cord blood of infants born to mothers on a normal sodium intake were significantly lower (P < 0.005) than those of infants whose mothers had required low sodium diet and/or diuretics during their pregnancy.Aldosterone concentrations in plasma of infants 1-72 hr of age and born to mothers on normal sodium intake were 25.9+/-11.7 ng/100 ml (mean +/-1 SD). These values were significantly lower (P < 0.005) than those of infants born to mothers on restricted sodium intake with or without diuretics (80.3+/-54.4 ng/100 ml). The concentrations at birth were not significantly different from those observed during the first 3 days of life (P > 0.6).     

Verapamil prolongs atrial fibrillation by evoking an intense sympathetic neurohumoral effect.

BACKGROUND: Verapamil is an effective drug to slow ventricular rate in atrial fibrillation (AF). Clinically, however, i.v. verapamil enhances AF despite experimental evidence suggesting favorable effects of the drug on AF-induced electrical remodeling of the atria. METHODS AND RESULTS: To clarify this controversy, i.v. verapamil's effects were determined in 41 anesthetized dogs, including 6 after beta-blockade. Intravenous verapamil (0.20 mg/kg, bolus, and 0.20 mg/kg/h, infusion) increased the duration of AF (induced by a single extrastimulus), from 19 +/- 6 to 130 +/- 24 s, P < 0.001, and slowed its ventricular response, from 246 +/- 25 to 110 +/- 15 min-1, P < 0.001. Mean aortic pressure, P = 0.002, and systemic vascular resistance, P < 0.035, decreased, and mean right atrial pressure increased, P < 0.001. Plasma norepinephrine concentration increased by 502 +/- 83 pg/mL, P < 0.001, plasma epinephrine concentration by 804 +/- 206 pg/mL, P = 0.002, and plasma total catecholamine concentration by 1606 +/- 366 pg/mL, P = 0.001. Prolongation of AF was related to an increase in mean right atrial pressure, R = 0.49, P = 0.014, right atrial wall tension, R = 0.45, P = 0.044, and plasma norepinephrine concentration, R = 0.83, P < 0.001, with plasma norepinephrine concentration remaining as an independent predictor of AF lengthening on multivariable analysis. In the presence of beta-blockade, verapamil produced comparable or more exaggerated hemodynamic effects, but it did not promote AF. CONCLUSION: The prolongation of AF by verapamil can be related directly to the intense sympathetic neurohumoral effect that occurs following the drug's administration.     

Increased conjugated dopamine in plasma after exercise training

To evaluate the effect of endurance exercise on plasma catecholamines, we exercise trained eight dogs (group T) by treadmill running for 8 weeks. Six sedentary dogs constituted a nontrained control group (group NT). Heart rate response to a graded submaximal stress test was reduced in group T dogs (p less than 0.05), but mean resting aortic blood pressure (NT, 84 +/- 5 mm Hg; T, 82 +/- 4 mm Hg) and heart rate (NT, 87 +/- 1 bpm; T, 84 +/- 2 bpm) were unchanged by exercise, and no cardiac hypertrophy occurred after exercise. Plasma norepinephrine and epinephrine levels were reduced in group T at rest and during a fixed exercise workload. Plasma conjugated dopamine showed a marked increase in group T dogs (NT, 1398 +/- 130 pg/ml; T, 11346 +/- 1291 pg/ml; p less than 0.01) at rest, and no change in conjugated dopamine occurred in either group after short-term exercise stress. No intergroup differences were noted in resting coronary flow or coronary arteriovenous oxygen, or in myocardial oxygen consumption. The data verify previous findings of lower plasma levels of norepinephrine and epinephrine after training, and indicate that a marked rise in conjugated dopamine occurs after training. These findings suggest that norepinephrine and epinephrine metabolism is shifted toward conjugated dopamine by exercise training, thereby reducing active catecholamines in plasma, but retaining a large pool of usable metabolite.     

Differential effects of carvedilol and metoprolol succinate on plasma norepinephrine release and peak exercise heart rate in subjects with chronic heart failure

Dosing equivalency of carvedilol and metoprolol remains a debate. Degree of beta 1-blockade is best assessed by blunting of the exercise-induced heart rate. Accordingly, the authors have investigated dosing equivalency by examining baseline and peak exercise heart rates and norepinephrine levels in subjects with chronic heart failure treated with carvedilol or metoprolol. Thirty-seven subjects treated with carvedilol (32.9 +/- 3.5 mg; n = 23) or metoprolol succinate (XL) (96.4 +/- 15.9 mg; n = 14) referred for cardiopulmonary exercise testing were studied prospectively. Carvedilol versus metoprolol XL subjects did not differ with respect to baseline heart rate (73 +/- 2 vs 70 +/- 3 bpm), or baseline plasma norepinephrine levels (597.5 +/- 78.3 vs 602.1 +/- 69.6 pg/mL), P = NS. However, despite similar peak exercise norepinephrine levels (2735.8 +/- 320.1 vs 2403.1 +/- 371.6 pg/mL), heart rate at peak exercise was higher in subjects receiving carvedilol (135 +/- 4 bpm) than those receiving metoprolol XL (117 +/- 6 bpm), P = 0.02. Similar norepinephrine release and more complete beta 1-blockade is observed in well-matched subjects with chronic heart failure treated with a mean daily dose of metoprolol XL 96.4 mg compared with carvedilol 32.9 mg.     

Emergency medical service transport-induced stress? An experimental approach with healthy volunteers

This randomized controlled trial was designed to evaluate the effects of simulated emergency medical service (EMS) transport related stress on hemodynamic variables, and catecholamine plasma levels. A total of 32 healthy male volunteers were randomized to being carried by paramedics from a third-floor apartment through a staircase with subsequent high-speed EMS transport with lights and sirens (stress; n = 16); or sitting on a chair for 5 min, and lying on a stretcher for 15 min (control; n = 16). Blood samples and hemodynamic variables were taken in the apartment before transfer, at the ground floor, and at the end of EMS transport in the stress group, and at corresponding time points in the control group. The stress versus control group had both significantly (P < 0.05) higher mean +/- SEM epinephrine (71 +/- 7 versus 37 +/- 3 pg/ml), and norepinephrine (397 +/- 29 versus 299 +/- 28 pg/ml) plasma levels after transport through the staircase. After EMS transport, the stress versus control group had significantly higher epinephrine (48 +/-6 versus 32 +/- 2 pg/ml), but not norepinephrine (214 +/- 20 versus 264 +/- 31 pg/ml) plasma levels. Heart rate increased significantly from 72 +/- 2 to 84 +/- 3 bpm after staircase transport, but not during and after EMS transport. In conclusion, volunteers being carried by paramedics through a staircase had a significant discharge of both epinephrine and norepinephrine resulting in increased heart rate, but only elevated epinephrine plasma levels during EMS transport. Transport through a staircase may reflect more stress than emergency EMS transport.     

Humoral mechanisms in the pathogenesis of postprandial hypotension in patients with essential hypertension

OBJECTIVE: To examine the role of catecholamines and insulin in the development of postprandial hypotension (PPH) in hypertensive patients. PATIENTS: Forty patients with essential hypertension (25 men, 15 women, mean age 68 +/- 2 years). METHOD: Blood pressure and heart rate were recorded in all subjects immediately after a 1903 kJ test meal and at 15-minute intervals for up to 1 hour after the meal. At these time points, circulating levels of norepinephrine, epinephrine, dopamine and C-peptide were measured. RESULTS: Twenty-three patients (58%) had PPH. By 15 minutes norepinephrine had significantly increased in PPH-negative subjects while it rose more slowly in PPH-positive patients and peaked by 45 minutes after the meal. Norepinephrine levels in 15 minutes were lower in PPH-positive than in PPH-negative ones (159.8 +/- 9.7 vs. 212.3 +/- 21.1 pg/ml, p = 0.01). Epinephrine levels rose only in PPH-negative subjects and did not differ significantly at the different time points. However, the area under curve analysis showed significantly lower epinephrine values in PPH-positive subjects (2903 + 247 pg.min.ml-1 vs. 3710 + 284 pg.min.ml-1, p = 0.03). Dopamine increased in both groups, although it was lower in subjects with PPH during the entire study (15 minutes: 68.6 +/- 3.7 vs. 93.7 +/- 11.7 pg/ml, p = 0.02; 30 minutes: 68.8 +/- 3.7 vs. 86.1 +/- 7.7 pg/ml, p = 0.03; 45 minutes: 60.5 +/- 4.2 vs. 79.7 +/- 5.2 pg/ml, p = 0.006). The postprandial C-peptide response did not differ between patients with PPH and those without PPH. CONCLUSIONS: In patients with essential hypertension, a marked decline in postprandial systolic blood pressure is associated with lower postprandial levels of norepinephrine, epinephrine and dopamine as compared to subjects without postprandial hypotension. This indicates that impaired sympatho-adrenal activation after ingestion of a meal may contribute to the development of PPH. Insulin appears not to be involved in the pathogenesis of postprandial hypotension.