To test whether propranolol may influence the progression of coronary atherosclerosis.

To determine if ammonium ion plays a role in the lactate and ventilatory thresholds of incremental exercise, we investigated the effects on blood lactate and ventilation of NH(4+)-buffering by monosodium glutamate. Six normal volunteers underwent intravenous loading with MSG, 9 g, in a randomized, double-blind, saline placebo controlled crossover study. Four of the six subjects had a greater than 10 percent fall in peak (NH4+) following MSG (37 +/- 2.0 vs 25 +/- 4.3 micrograms/dl p = 0.003, PLB vs MSG). When MSG blunted the rise in venous (NH4+) during exercise, uncoupling of the LT and VT was observed. Specifically, with suppression of peak exercise (NH4+) by MSG, the LT was delayed (r = -0.84, p = 0.03), the VT was earlier (r = 0.86, p = 0.02), and the VO2 difference between the LT and VT widened (r = -0.90, p = 0.02). We conclude that NH4+ plays a role in determining the LT and VT of incremental exercise and that the VT may not be exclusively dependent on blood lactate.

We compared the hemodynamic effects of three different ventilatory patterns including two variations of the I:E ratio (2:1 and 3:1) and a PEEP-pattern with the MAWP being equal in all three patterns. The study was performed on 15 patients without lung or cardiovascular disease who were ventilated after elective abdominal surgery. Each of the patients was subjected to the three different pressure wave curves. The IPPV served as control. Hemodynamic measurements included TEE registration of the LV cross-sectional areas, diameters and wall thickness as well as arterial blood pressure and heart rate. As a result, we found no significant differences in the hemodynamic effects of all three patterns. Compared with IPPV, they showed a reduction of systolic and diastolic blood pressure, LV dimensions and systolic wall stress. Assessed with the end systolic quotient, LV contractility remained constant.

We evaluated nasal anesthesia regimens by comparing, in seven normal men, four drug regimens: 1) 1 percent phenylephrine; 2) 4 percent lidocaine; 3) 1 percent phenylephrine + 4 percent lidocaine; and 4) 5 percent cocaine. After spraying each drug into the anterior nares, vasoconstriction, decongestion, and nasal anesthesia (measured as transnasal depth of nasogastric (NG) tube insertion before discomfort) were assessed. There were no significant differences in NG tube insertion depth between the regimens (p = 0.54). Insertion depth was significantly increased after 10 ml of 2 percent viscous lidocaine were sniffed (p less than 0.004), but again, differences between regimens were not significant (p = 0.051). One hundred bronchoscoped patients received one of the following sprayed into the nose: 1) placebo (P); 2) 1 percent phenylephrine + P; 3) 1 percent phenylephrine + 4 percent lidocaine; or 4) 5 percent cocaine + P. Each patient then sniffed viscous lidocaine. There were no significant differences between regimens for any of the following: 1) nasal resistance to bronchoscope insertion, 2) patient's nasal discomfort, or 3) bronchoscopist's perception of patient discomfort. We conclude that sprayed anesthetics contribute little to nasal anesthesia and any regimen appears acceptable when viscous lidocaine is used.

To evaluate the effect of long-term bronchodilator therapy in CF patients with demonstrated bronchial hyperresponsiveness, we first performed methacholine challenges to determine responsiveness, then entered 27 patients (16 methacholine responders and 11 nonresponders) into a two-month double-blind crossover trial of albuterol, 90 micrograms by inhalation four times a day vs placebo. Among the responders, daily PEFR measures improved significantly more during treatment with albuterol (12 +/- 32 L/min) than with placebo (-0.4 +/- 19 L/min; p less than 0.05). In addition, a clinically important level of improvement in PEFR (15 percent increase) was reached significantly more frequently in the responders. Methacholine nonresponders had no change in PEFR on either albuterol or placebo. Daily symptom scores as well as spirometry measurements at biweekly visits did not show significant changes. We conclude that long-term therapy with inhaled albuterol improves lung function in CF patients, but only in those with bronchial hyperresponsiveness as demonstrated by methacholine challenge.

Conflicting reports have appeared concerning the role of anticholinergic agents in the treatment of acute asthma. This study was designed to determine whether atropine sulfate, the only anticholinergic agent currently available in the United States for nebulization, increases bronchodilation when added to an inhaled beta-adrenergic agonist during the initial treatment of an acute asthma attack. Adults asthmatics (n = 40) with acute asthma attacks were randomized to receive metaproterenol (5 percent solution, 0.3 ml) either alone or with atropine sulfate (2.5 mg), by nebulization. Spirometry, vital signs, and the presence of side effects 0, 30, 60, and 120 minutes after treatment were determined. There were no significant differences between the metaproterenol alone and metaproterenol plus atropine sulfate groups in regard to age, duration of asthma, baseline spirometry, or side effects. No differences were noted between the two groups regarding changes in FEV1 and FVC from baseline (expressed in milliliters or as a percentage of baseline) during the observation period. We conclude that nebulized atropine sulfate yields no additional benefit when added to metaproterenol during the initial treatment of an acute asthma attack.

This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical.

Intravenous conjugated estrogens correct bleeding times and reduce bleeding in uremia, gastrointestinal telangiectasias, and liver disease. One study found a similar benefit in patients undergoing open heart surgery. The mechanism by which conjugated estrogens improve bleeding times is unknown. We report on the effect of estrogens on endothelial prostacyclin production and bleeding in coronary bypass surgery. In a randomized, double-blind trial, 16 male patients undergoing elective coronary artery bypass surgery received four daily infusions of conjugated estrogens (0.6 mg/kg/day) or placebo, preoperatively. Groups were similar with respect to age, preoperative hemostatic profiles, and pump time. Conjugated estrogens significantly reduced greater saphenous vein endothelial prostacyclin production in the estrogen group compared to control subjects. Postoperative blood loss was not reduced, with a trend toward increased blood loss in the treatment group. We have shown that conjugated estrogens reduce endothelial prostacyclin production and fail to reduce blood loss in coronary bypass surgery.

Hemodynamic and oxygen transport effects of PGE1 were observed in the early postoperative period before development of ARDS in two series of general surgical patients with circulatory deficiencies. The first was a series of 19 studies in 18 patients, the second was a placebo-controlled series of 20 patients (ten received PGE1 and ten received a placebo). In the first series, PGE1 was given as a trial of therapy after fluid therapy to pulmonary wedge pressures greater than 15 mm Hg failed to correct satisfactorily circulatory and metabolic functions. There were two deaths in the placebo group and none in the PGE1 group. Previous studies indicated that PGE1 disaggregates platelets and reduces local vasoconstriction in pulmonary circulation; this study suggests that PGE1 improves tissue perfusion of systemic circulation. After fluid therapy to PAOP greater than 15 mm Hg fails to restore circulatory function to optimal values. PGE1 should be considered as ancillary therapy in critically ill postoperative patients.

Platelet-activating factor (PAF) is an inflammatory mediator capable of inducing protracted inflammation of the airways and bronchial hyperreactivity. Twenty-one asthmatic children were evenly divided into three groups and each group performed a double-blind, placebo-controlled and crossover study on the effect of aerosolized BN52021, a PAF antagonist, on the bronchoconstriction induced by PAF, methacholine, or specific allergen, respectively. One group of healthy children was included for comparison. Total WBC, neutrophils, and eosinophils were counted before and after PAF challenge. The results showed the following: (1) six of seven asthmatics and one of seven normal subjects gave a positive bronchial provocation with PAF; (2) in asthmatics, prior inhalation of BN52021 could inhibit the bronchoconstriction induced by PAF (6/6) and allergen (3/7), but not by methacholine; and (3) 5 min after inhalation of PAF, there was a marked decrease of peripheral blood eosinophils and neutrophils that could be inhibited by prior inhalation of BN52021 in normal subjects but not in asthmatics. These findings support the idea that PAF may be involved in the pathogenesis of bronchial asthma and PAF antagonist may have a role in the prevention and treatment of this disease.

The hemodynamic and oxygen transport effects of low-dose (0.75 mg/kg loading dose + 10 micrograms/kg/min infusion, n = 12) and high-dose (2.25 mg/kg loading dose + 20 micrograms/kg/min infusion, n = 12) amrinone were evaluated in extubated patients 24 h after CABG. At both doses, amrinone significantly (p less than 0.05) increased HR, but decreased mean arterial, mean pulmonary artery, central venous and pulmonary artery occlusion pressures. High-dose amrinone significantly decreased systemic vascular resistance. Arterial oxygen saturation decreased significantly following both low- (97.8 +/- 0.4 to 95.6 +/- 0.9 percent) and high- (98.8 +/- 3.4 to 93.9 +/- 1.2 percent) dose amrinone. Pulmonary shunt increased significantly following low-dose amrinone and markedly increased Qs/Qt after high-dose amrinone. Although amrinone significantly increased cardiac index in a dose-dependent fashion (low:3.0 +/- 0.2 to 3.3 +/- 0.3 L/min/m2; high:2.7 +/- 0.2 to 3.4 +/- 0.2 L/min/m2), mixed venous oxygen saturation did not change. Thus, mixed venous oxygen saturation may not predict the hemodynamic response to amrinone infusion in postoperative surgical patients.

In a randomized study in 26 elderly patients with mild essential hypertension, acute effects of alpha- and beta-adrenoceptor blockade on plasma ANP levels were examined at rest and during ergometric exercise. Plasma ANP level and LVEF were measured before and after administration of prazosin (an alpha 1-adrenergic blocker), atenolol (a cardioselective beta-adrenergic blocker), or carteolol (a nonselective beta-adrenergic blocker). Plasma ANP level was increased by exercise. Carteolol and atenolol increased plasma ANP levels at rest and during exercise, but the effect of atenolol was not statistically significant. Prazosin significantly suppressed the ANP values at rest and during exercise. The LVEF was increased by prazosin and decreased by beta-blockers, especially by carteolol. Multivariate regression analysis showed that LVEF was the most significant predictor of the plasma ANP level at maximal exercise; the resting blood pressure and heart rate were not predictors of this value. The results showed that single administrations of an alpha-blocker and a nonselective beta-blocker had opposite effects on the plasma ANP level both at rest and during exercise in elderly patients with mild essential hypertension. The observed difference in the ANP response seems to be related to changes in left ventricular function rather than changes in blood pressure or heart rate.

Patients with COPD may respond differently to anticholinergic and beta-agonist bronchodilators. Previously, in acutely ill COPD patients, we showed similar improvements in pulmonary function after each drug (study 1). The responses of the same patients when stable are now reported (study 2). Patients received ipratropium bromide (54 micrograms) (n = 16) or metaproterenol sulfate (1.95 mg) (n = 14) via an MDI attached to a delivery device as in study 1. Ninety minutes after the first medication, patients received the second. Spirometry was measured at entry and at 30-min intervals following the first drug and at the same times after the second drug. Results were as follow: The groups did not differ in clinical characteristics. However, for both groups, there was significantly less airway obstruction at entry into study 2. In study 1, ipratropium resulted in significant improvement in FEV1 (0.62 +/- .08 to 0.88 +/- .11 L; mean increase 24 percent; p less than 0.05) with no further change after crossover. In study 2, ipratropium produced similar improvements in FEV1 by 90 minutes (0.94 +/- .09 to 1.3 +/- .09 L; mean increase 25 percent; p less than 0.05), with no further improvement after crossover. For metaproterenol, in study 1, the improvement in FEV1 was not significantly different than that for ipratropium (FEV1; 0.71 +/- .07 to 0.92 +/- 0.06 L; mean increase 18 percent; p less than 0.05), with no further improvement after crossover. In study 2, improvement with metaproterenol was significant and similar to study 1 (FEV1: 0.96 +/- .06 to 1.21 +/- .09 L; mean increase 18 percent; p less than 0.05). Thus, ipratropium and metaproterenol similarly improved pulmonary function in COPD patients when stable and during acute exacerbations.

We evaluated effects of duodenojejunal (DJ) feeding on gastric pH and selected gastrointestinal hormones in 13 randomly selected patients in an intensive care unit (ICU). To obtain baseline values for gastric pH, a nasogastric (NG) tube was placed in each patient and gastric pH was measured every 30 minutes for 2 hours. To obtain control values, a Dobbhoff tube was placed fluoroscopically and 0.45 percent saline solution (NaCl), 75 ml, was infused for 1 hour and gastric pH was measured again; the previously placed NG tube was left in position. Then, by randomization, either 0.45 percent NaCl (pH = 5) was continued (n = 6) or a high-nitrogen, isotonic, enteral feeding solution (Osmolite HN, pH = 6.4) (n = 7) was infused, both at 75 ml/h. Gastric pH was noted hourly for 96 hours; antacid (Maalox TC, 15-ml aliquots) was given by NG tube when the pH was 4 or less. After 96 hours, the infusion was stopped and gastric pH was noted for 4 additional hours. Before and during initial saline solution infusion; after 24, 48, 72, and 96 hours of continuous infusion; and 4 hours after stopping the infusion, peripheral venous blood was obtained for measurement of plasma gastric inhibitory polypeptide (GIP) and serum gastrin. Data were analyzed by ANOVA (RMD), Fishers' exact test, and the unpaired t-test. Groups did not differ demographically. Throughout the infusion, gastric pH tended to be higher with the enteral feeding solution than with saline solution, but this was significant only at 24 hours. Less antacid was required with the enteral feeding solution at 24 and 48 hours than with saline solution. Plasma GIP levels were significantly higher with the enteral feeding solution than with saline solution during most of the infusion. Serum gastrin levels did not differ between the groups. In this cohort, infusion of the enteral feeding solution tended to maintain a gastric pH of more than 4 and was associated with increased plasma GIP levels, which may inhibit gastric acid secretion. Early enteral feeding may benefit certain ICU patients.

Intralipid (20 percent, 500 ml) was infused fast (5 h) or slow (10 h) randomly in patients with lung injury to relate changes in plasma prostaglandin (PG) concentrations to gas exchange and pulmonary hemodynamics. Data were collected at baseline, midpoint of infusion, and 2 h following infusion. Vasodilator and vasoconstrictor PG metabolites, 6-keto-PGF1 alpha, and thromboxane B2, respectively, were measured in radial arterial blood samples. Slow Intralipid infusion increased shunt fraction (QS/QT) without changing mean pulmonary artery pressure (MPAP), whereas fast Intralipid infusion increased MPAP without changing QS/QT. Prostaglandin levels did not change significantly during either infusion. However, in both groups when the PG substrate was removed, hemodynamic and metabolite values decreased in parallel. In conclusion, we were unable to demonstrate a cause and effect relationship between plasma levels of 6-keto-PGF1 alpha and thromboxane B2 and the observed pulmonary hemodynamic response to slow or fast Intralipid infusion.

In a double-blind, randomized, multicenter study, the efficacy and safety of intravenous (IV) nicardipine was compared with placebo in the control of postoperative hypertension in cardiac and noncardiac surgical patients. One hundred twenty-two patients (17 cardiac and 105 noncardiac surgery) met the entry criteria (systolic BP greater than or equal to 140 mm Hg or diastolic BP greater than or equal to 95 mm Hg) and were randomized (3:2) to receive IV nicardipine (n = 71) or placebo (n = 51). Therapeutic response (greater than or equal to 15 percent reduction in BP from baseline) was achieved in 94 percent of patients treated with IV nicardipine vs 12 percent with placebo (p less than 0.001). The mean response time and infusion rate for IV nicardipine were 11.5 (+/- 0.8) minutes and 12.8 (+/- 0.3) mg/h, respectively. The magnitude of BP reduction was similar in both cardiac and noncardiac postsurgical patients. Blood pressure control was sustained with minimal dose adjustments of IV nicardipine (3.0 +/- 0.2 mg/h) during a prolonged maintenance infusion period of 6.8 +/- 0.5 h. A reflex mean increase in heart rate of 5 bpm was seen in patients treated with IV nicardipine. Sixteen patients (15 noncardiac and one cardiac surgery) had a sustained heart rate of greater than 100 bpm, with a mean increase of 24 bpm from the baseline. In all these patients except three, tachycardia was resolved while receiving nicardipine. None of these patients who had development of tachycardia during nicardipine therapy had exhibited ST segment changes indicative of ischemia. One patient with tachycardia at baseline had exhibited ST segment depression (3 to 4 mm) during nicardipine treatment, which was resolved following discontinuation of nicardipine therapy and application of nitroglycerin (Nitropaste). Hemodynamic evaluation revealed that IV nicardipine significantly decreased mean arterial pressure, systemic vascular resistance, and significantly increased cardiac index with no change in heart rate. These hemodynamic changes were similar in cardiac and noncardiac surgical patients. Adverse experiences reported with IV nicardipine included hypotension (4.5 percent), tachycardia (2.7 percent), and nausea/vomiting (4.5 percent). In the placebo group, the incidence of adverse experience was 6 percent, with an equal distribution of hypotension (2 percent), nausea/vomiting (2 percent), and headache (2 percent). No clinically important changes in laboratory variables related to IV nicardipine were reported. In conclusion, these findings indicate that nicardipine, a titratable intravenous calcium channel blocker, can rapidly and effectively control postoperative hypertension in cardiac and noncardiac surgical patients.

Pilot study to determine if the presence of antibody-coated bacteria (ACB) in sputum specimens obtained from endotracheal tube suctioning would aid in the diagnosis of lower respiratory tract infection (LRTI).

We determined the relative efficacy of two bronchodilator aerosol delivery methods in 18 intubated mechanically ventilated patients with airways obstruction. Two treatment arms, consisting of albuterol 270 micrograms (three puffs) from a metered dose inhaler and albuterol 2.5 mg from a saline solution nebulized with an updraft inhaler, were compared in a single blind, randomized crossover design. Pulmonary function was evaluated using an interrupter technique. Changes in passive expiratory flow at respiratory system recoil pressures between 6 and 10 cm H2O provided the therapeutic endpoints. Paired measurements were made before and 30 minutes after drug delivery. The MDI and NEB resulted in similar improvements in iso-recoil flow (mean increase for both groups = 0.1 L/s). Treatment sequence, severity of obstruction, and bronchodilator responsiveness had no effect on relative efficacy. Albuterol caused a small but significant increase in heart rate that was similar following both delivery methods. We conclude that bronchodilator aerosol delivery with metered dose inhalers provides a viable alternative to nebulizer therapy in intubated mechanically ventilated patients and may result in a cost savings to hospitals and patients.

Fifty-two patients were randomized to receive either incentive spirometry (IS) or intermittent positive pressure breathing (IPPB) in addition to conventional chest physical therapy following coronary artery bypass grafting. Slow vital capacity and peak expiratory flow readings decreased rapidly and to an equal extent in both groups after surgery, and partly recovered by the sixth postoperative day (POP). Arterial PO2 values were similar for the groups on the first three POPs. On the POPs 2, 3, and 6, the number of chest films showing atelectases as well as the number of individual patients having atelectases revealed no statistically significant differences between the two groups. Based on the three variables studied, we consider both devices equal in efficiency after coronary surgery.