Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

OBJECTIVE: This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. DESIGN: Prospective, nonrandomized study. SETTING: Operating room in a university hospital. PATIENTS: Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. METHODS: Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. MEASUREMENTS AND MAIN RESULTS: The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. CONCLUSIONS: Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.     

Effects of cocaine alone and in combination with bromocriptine in human cocaine abusers.

This study was conducted to determine whether the acute administration of bromocriptine, a dopamine agonist, modulates the acute pharmacologic effects of i.v. cocaine in humans. Eight current users of i.v. cocaine who were not seeking treatment for their cocaine abuse completed the study while they were inpatients on a research unit. Twelve drug conditions were tested in all subjects in randomized order under double-blind, double-dummy conditions and included cocaine (0, 12.5, 25 and 50 mg, i.v.) in combination with bromocriptine (0, 1.2 and 2.5 mg given orally 2 hr before the cocaine injection). Physiologic and subject- and observer-rated responses were measured. Cocaine alone significantly increased pupil diameter, heart rate and blood pressure, and ratings of drug effect, good effects, liking and rush. Bromocriptine alone significantly increased pupil diameter and heart rate, decreased blood pressure and had only minor effects on subjective measures. There were significant cocaine/bromocriptine interactions on diastolic and mean arterial blood pressure, with combinations producing significantly smaller increases compared to cocaine alone, and on heart rate, with combinations producing significantly larger increases compared to cocaine alone. The physiologic and subjective effects of cocaine were not modified by pretreatment with bromocriptine in any other way that might indicate either a therapeutic benefit or a safety concern. However, bromocriptine alone produced undesirable effects (fainting) that should be considered before administration to outpatient cocaine abusers. Any possible therapeutic benefits of acute administration of bromocriptine in cocaine abuse are not likely to be due directly to modulation of the acute effects of cocaine.     

2,6-Diamino-N-([1-(1-oxotridecyl)-2-piperidinyl] methyl)hexanamide (NPC 15437): a novel inhibitor of protein kinase C interacting at the regulatory domain.

NPC 15437 is a prototype member of a new class of synthetically derived protein kinase C (PKC) inhibitors. PKC activity and binding of phorbol ester to the enzyme were inhibited by NPC 15437, with IC50 values of 19 +/- 2 microM and 23 +/- 4 microM, respectively. No inhibition of cAMP-dependent or calcium/calmodulin-dependent protein kinases was observed at concentrations of NPC 15437 up to 300 microM. To investigate the mechanism by which NPC 15437 exerts its effects, a kinetic analysis of the inhibition with respect to three activators of the enzyme, phosphatidylserine, calcium, and phorbol ester, was performed. NPC 15437 was a competitive inhibitor of the activation of PKC by phorbol ester (Ki = 5 +/- 3 microM). Stimulation of PKC alpha by phosphatidylserine was competitively inhibited by NPC 15437 (Ki = 12 +/- 4 microM). The inhibition was mixed with respect to activation by calcium. These results suggest that NPC 15437 is a selective inhibitor of PKC, interacting at the regulatory region of the enzyme. NPC 15437 inhibited PKC in intact cells, dose-dependently antagonizing the phorbol ester-induced phosphorylation of a 47-kDa protein in human platelets.     

The effect of total arterial grafting on medium-term outcomes following coronary artery bypass grafting

Background  

While it is believed that total arterial grafting (TAG) for coronary artery bypass grafting (CABG) confers improved long-term outcomes when compared to conventional grafting with left internal mammary artery and saphenous vein grafts (LIMA+SVG), to date, this has not become the standard of care. In this study, we assessed the impact of TAG on medium-term outcomes after CABG.     

Don’t Let an Opportunity Go by: Validation of the EIGHT Gambling Screen

The EIGHT Screen is a brief problem gambling screen originally designed for use by family doctors. Its wider use indicated the need for further validation. A triangulated approach used a range of measures in different settings in both the current study and findings from a number of earlier projects, and reviewed current use. The EIGHT Screen had acceptable correlations with the SOGS (r = 74–90%) and with the NODS-12 months Screen (r = 62.4%). Measurements remained relatively constant amongst a range of cultures, settings, age and gender, while few false positives were produced by the screen. The EIGHT Screen appears to be a valid tool for untrained users to identify Level 2 and 3 problem gambling in a wide range of cultures and settings.