Patients with stable coronary disease do not have the normal vasodilator response to intracoronary serotonin, but rather have progressive constriction, which is particularly intense in small distal and collateral vessels. Patients with variant angina have occlusive coronary-artery spasm at a dose that dilates normal vessels and causes only slight constriction in vessels from patients with stable angina. These findings suggest that serotonin, released after the intracoronary activation of platelets, may contribute to or cause myocardial ischemia in patients with coronary artery disease.
Communicated by Charles G. Sibley, November 30, 1992 ABSTRACT Elevated blood levels of apolipoprotein(a), the component of lipoprotein(a) that distinguishes it from low density lipoprotein, are a major risk factor for atherosclerosis. The apolipoprotein(a) gene is highly similar to the pasminogen gene and to at least four other genes or pseudogenes. The 5' untranslated and flanking sequences of these six genes contain
Endothelin, a 21-amino acid peptide synthesized by cultured porcine aortic endothelial cells, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. We have studied the effect of local infusion of this peptide on resistance and capacitance vessels of normal volunteers. Infusion of endothelin (5 pmol/min) reduced forearm blood flow by 39 +/- 7% from control observations. The maximum response was seen after approximately 55 min of infusion. After stopping the infusion, return of flow to basal values took approximately 120 min. This contrasts with the short onset and duration of action observed when angiotensin II was infused. During coinfusion studies, reversal by nicardipine (0.3-10 micrograms/min) occurred at similar concentrations in both endothelin-induced and angiotensin-induced flow reduction. This observation suggests that nicardipine nonspecifically antagonizes the flow-reducing effects of endothelin. A pattern of slow onset of constriction was found on local infusion of endothelin (5 pmol/min) into dorsal hand veins. During coinfusion of nicardipine (1.5 microgram/min), no reversal of endothelin-induced (5 pmol/min) constriction of dorsal hand veins occurred. The pharmacological profile of this peptide in the peripheral circulation of humans suggests that it may be involved in long-term regulation of vascular tone.
AimTo determine the separate effects of exercise amount and intensity on the rate of response for glucose and insulin variables, where rate of response was defined as the number of individuals with improvement in glucose and insulin values that was beyond the day-to-day variability of measurement.MethodsParticipants were 171 sedentary, middle-aged abdominally obese adults who completed a 24-week intervention. Participants were randomly assigned to (1) no-exercise control (n = 51), (2) low-amount, low-intensity exercise (LALI, n = 38), (3) high-amount, low-intensity exercise (HALI, n = 52), or (4) high-amount, high-intensity exercise (HAHI, n = 30). Two-hour glucose, insulin area under the curve (AUC), and fasting insulin were measured during a 2-hour, 75g oral glucose challenge. The day-to-day variability for these measures was calculated to be ±2.2 mmol/L, ±940.2 pmol/L, and ±38.9 pmol/L, respectively.ResultsAt 24 weeks, the number of nonresponders for 2-hr glucose was 98.0%, 86.8%, 94.2%, 86.7% in the control, LALI, HALI, and HAHI groups, respectively. The number of nonresponders for insulin AUC was 88.0%, 75.7%, 75.0%, 80.0% in the control, LALI, HALI, and HAHI groups, respectively. The number of nonresponders for fasting insulin was 88.2%, 84.2%, 84.6%, 93.3% in the control, LALI, HALI, and HAHI groups, respectively. The rate of response was not different between control and any of the exercise groups for any measure (p>0.05).ConclusionThe improvement in glucose and insulin measures did not exceed the day-to-day variability of measurement for approximately 80% of the participants independent of exercise amount or intensity.
To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients. DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients. DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I 2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C. CONCLUSIONS:IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.
Objective To determine the effects of exercise amount (kilocalories per session) and intensity (percent of maximal oxygen consumption [% VO2peak]) on adipose tissue (AT) and skeletal muscle (SM) in adults with abdominal obesity. Methods Participants (n = 103; 52.7 ± 7.6 years) were randomized to the following groups: control; low‐amount, low‐intensity exercise (180 kcal/session [women] and 300 kcal/session [men] at 50% VO2peak); high‐amount, low‐intensity exercise (HALI; 360 kcal/session [women] and 600 kcal/session [men] at 50% VO2peak); or high‐amount, high‐intensity exercise (HAHI; 360 kcal/session [women] and 600 kcal/session [men] at 75% VO2peak) for 24 weeks. Activities of daily living were measured by accelerometry. Magnetic resonance imaging was used to measure tissue mass. Results Reduction in all AT depots was greater in the exercise groups compared with control (P < 0.002); however, there were no differences between exercise groups (P > 0.05). Visceral and abdominal subcutaneous AT reduction was uniform across the abdomen. Total SM mass did not change with exercise compared with control (P = 0.32). However, while lower‐body SM mass was maintained (P = 0.32), upper‐body SM mass in the high‐amount, high‐intensity and the high‐amount, low‐intensity groups was reduced compared with controls (P < 0.008). Conclusions In adults with abdominal obesity, substantial reductions in total, abdominal subcutaneous, and visceral AT with a preservation of total SM mass were observed independent of exercise amount or intensity.
BACKGROUND Serotonin, released by aggregating platelets, may contribute to or cause myocardial ischemia by constricting epicardial vessels. Experimental studies suggest that this constriction is mediated by two distinct serotonin receptor subtypes: 5-hydroxytryptamine1-like (S1-like) and 5-hydroxytryptamine2 (S2). METHODS AND RESULTS To determine the relative contribution of S1-like and S2 receptors to the vasoconstrictor effects of serotonin, we studied the effect of ketanserin (0.75 mg, intracoronary), a selective S2 receptor antagonist, on the constrictor response of human coronary vessels to intracoronary infusions of serotonin. In control patients (n = 7), serotonin (10(-4) mol/l) caused significant (p less than 0.05) constriction only in distal segments, which was significantly (p less than 0.05) inhibited by ketanserin. In stable angina patients (n = 8), serotonin (10(-4) mol/l) caused significant constriction in proximal (p less than 0.01) and distal (p less than 0.01) segments, which was significantly inhibited by ketanserin in proximal (p less than 0.05) but not distal (p = 0.30) segments. In patients with variant angina (n = 3), epicardial occlusion at the site of preexisting stenoses in proximal locations occurred at infused concentrations of 10(-6) (one patient) or 10(-5) (two patients) mol/l. The infusion of the same concentration of serotonin after ketanserin again caused epicardial occlusion. CONCLUSIONS Our results suggest that functionally important S1-like receptors that mediate vasoconstriction exist in the epicardial vessels of patients with stable or variant angina. Their activation, either at hyperreactive sites in patients with variant angina or in the distal epicardial vessels of patients with chronic stable angina, may contribute to or cause myocardial ischemia when serotonin is released after the intracoronary activation of platelets.
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