Effect of genetic variation in P2Y12 on TRAP-stimulated platelet response in healthy subjects.

In platelets, thrombin receptor signaling depends upon the release of adenosine diphosphate and subsequent activation at purinergic subtype Y (P2Y) receptors. The purpose of this study is to evaluate the influence of specific P2Y12 polymorphisms on platelet reactivity in healthy subjects mediated by thrombin receptor activating peptide (TRAP). We recruited a total of 29 healthy volunteers who had been previously genotyped for two polymorphisms of the P2Y12 receptor: the H2 haplotype (rs2046934) and 34C>T (rs6785930).

Pharmacodynamic interplay of the P2Y(1), P2Y(12), and TxA(2) pathways in platelets: the potential of triple antiplatelet therapy with P2Y(1) receptor antagonism.

Introduction: Previous work suggests that the extent of platelet inhibition by P2Y(1) receptor antagonism may be underappreciated, particularly in the context of dual antiplatelet therapy with aspirin and clopidogrel.

Materials And Methods: Using P2Y(1), P2Y(12), and TxA(2) receptor antagonists individually and in combination, we assessed the incremental changes from baseline platelet reactivity in blood collected from healthy volunteers.

Results: The P2Y(1) receptor antagonist further inhibited platelet activation and aggregation in several assay conditions ex vivo when combined with P2Y(12) and/or TxA(2) receptor blockers.

The dangers of gathering data: surgeon-specific outcomes revisited.

The accuracy of risk adjustment is important in developing surgeon profiles. As surgeon profiles are obtained from observational, nonrandomized data, we hypothesized that selection bias exists in how patients are matched with surgeons and that this bias might influence surgeon profiles. We used the Society of Thoracic Surgeons risk model to calculate observed to expected (O/E) mortality ratios for each of six cardiac surgeons at a single institution.

Antiplatelet drugs: mechanisms and risks of bleeding following cardiac operations.

Preoperative antiplatelet drug use is common in patients undergoing coronary artery bypass grafting (CABG). The impact of these drugs on bleeding and blood transfusion varies. We hypothesize that review of available evidence regarding drug-related bleeding risk, underlying mechanisms of platelet dysfunction, and variations in patient response to antiplatelet drugs will aid surgeons as they assess preoperative risk and attempt to limit perioperative bleeding.

The relationship between mortality and preexisting cardiac disease in 5,971 trauma patients.

Background: We observed significant morbidity and mortality in patients with preexisting cardiac disease who suffer severe traumatic injuries. We wondered about the types of injury seen and about the cardiac risks factors that predispose to worse outcomes in these patients. Our hypothesis is that significant cardiac comorbidity is associated with adverse trauma outcomes.

Pharmacokinetics and pharmacodynamics of a bolus and infusion of cangrelor: a direct, parenteral P2Y12 receptor antagonist.

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cangrelor administered as an intravenous bolus plus a continuous infusion in healthy volunteers. Twenty-two healthy volunteers are randomized to receive 1 of 2 intravenous cangrelor dosing regimens: a 15-microg/kg bolus followed by a 2-microg/kg/min infusion or a 30-microg/kg bolus followed by a 4-microg/kg/min infusion. The infusion is continued for 60 minutes, and serial blood samples are obtained for evaluation of pharmacokinetic and pharmacodynamic parameters.

Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect.

Background: Cangrelor is a direct, parenteral, and reversible inhibitor of the platelet P2Y12 receptor currently undergoing Phase III testing. As many individuals treated acutely with cangrelor will often be treated long-term with a thienopyridine, it is important to determine the effects of concurrent cangrelor and clopidogrel administration.

Methods And Results: Ten healthy volunteers received a 600 mg oral loading dose of clopidogrel and then underwent serial platelet function monitoring for 6 h.

Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.

Background: A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes.

The preischemic combination of the sodium-hydrogen exchanger inhibitor cariporide and the adenosine agonist AMP579 acts additively to reduce porcine myocardial infarct size.

Background: We tested whether the combination of two known cardioprotective agents, the type-1 sodium-hydrogen exchanger inhibitor cariporide plus the adenosine A(1)/A(2a) receptor agonist AMP579 ([1S-[1a,2b,3b, 4a(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-[(3)H]-imidazo[4,5-b]pyridyl-3-yl]cyclopentane carboxamide), acted additively to reduce myocardial infarct size.

Study Design: Pigs underwent 1 hour of coronary artery occlusion and 3 hours reperfusion. Vehicle-treated controls were compared with animals treated before ischemia with low-dose and high-dose cariporide and AMP579, and low-dose cariporide plus AMP579.

Assessing the medical literature: let the buyer beware.

As many as 30% of journal articles may contain errors. Most of these errors involve the use of simple statistical tests or elementary principles of research design. Assessment of the thoracic surgical literature involves cautious circumspection.

Aspirin and postoperative bleeding after coronary artery bypass grafting.

Objective: To evaluate the relationship between aspirin ingestion and postoperative bleeding complications, and to test the hypothesis that there is a subset of patients who are aspirin hyperresponders with a proclivity toward platelet dysfunction.

Summary Background Data: Despite numerous retrospective and prospective analyses, it is still controversial as to whether aspirin ingestion before coronary artery bypass grafting (CABG) is associated with significant postoperative bleeding.

Methods: Between January 1995 and December 1999, the records of 2,606 consecutive patients undergoing CABG were reviewed to identify patients with a history of aspirin ingestion up until the time of surgery.