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Adenosine myocardial protection: preliminary results of a phase II clinical trial
R M Mentzer1, V Birjiniuk, S Khuri
1Department of Surgery, University of Kentucky College of Medicine, Lexington 40526-0298, USA.
Objective:
To evaluate the safety, tolerance, and efficacy of adenosine in patients undergoing coronary artery bypass surgery.
Summary Background Data:
Inadequate myocardial protection in patients undergoing coronary artery bypass surgery contributes to overall hospital morbidity and mortality. For this reason, new pharmacologic agents are under investigation to protect the regionally and globally ischemic heart.
Methods:
In a double-blind, placebo-controlled trial, 253 patients were randomized to one of three cohorts. The treatment arms consisted of the intraoperative administration of cold blood cardioplegia, blood cardioplegia containing 500 microM adenosine, and blood cardioplegia containing 2 mM adenosine. Patients receiving adenosine cardioplegia were also given an infusion of adenosine (200 microg/kg/min) 10 minutes before and 15 minutes after removal of the aortic crossclamp. Invasive and noninvasive measurements of ventricular performance were obtained before, during, and after surgery.
Results:
The high-dose adenosine cohort was associated with a trend toward a decrease in high-dose dopamine support and a lower incidence of myocardial infarction. A composite outcome analysis demonstrated that patients who received high-dose adenosine were less likely to experience one of five adverse events: high-dose dopamine use, epinephrine use, insertion of intraaortic balloon pump, myocardial infarction, or death. The operative mortality rate for all patients studied was 3.6% (9/253).
Conclusions:
Adenosine treatment is safe and well tolerated and may be associated with fewer postoperative complications.
Insights
Adenosine cardioplegia administration during coronary artery bypass surgery appears safe and well-tolerated, potentially reducing postoperative complications like myocardial infarction and the need for intensive support. This cardiac protection strategy warrants further investigation.
Area of Science:
- Cardiology
- Cardiac Surgery
- Pharmacology
Background:
- Myocardial protection is crucial during coronary artery bypass surgery (CABS) to reduce morbidity and mortality.
- Inadequate protection of the ischemic heart remains a significant challenge in cardiac procedures.
- Investigational pharmacologic agents are being explored for enhanced myocardial protection.
Purpose of the Study:
- To assess the safety, tolerance, and efficacy of adenosine as a myocardial protective agent during CABS.
- To evaluate adenosine's impact on postoperative complications and ventricular performance.
Main Methods:
- A double-blind, placebo-controlled trial involving 253 patients undergoing CABS.
- Patients were randomized to receive cold blood cardioplegia, cardioplegia with 500 microM adenosine, or cardioplegia with 2 mM adenosine.
- Adenosine infusion was administered perioperatively, with ventricular performance monitored invasively and noninvasively.
Main Results:
- High-dose adenosine showed a trend towards decreased high-dose dopamine support and reduced myocardial infarction incidence.
- A composite analysis indicated fewer adverse events (e.g., high-dose dopamine, epinephrine, intra-aortic balloon pump, myocardial infarction, death) in the high-dose adenosine group.
- Overall operative mortality was 3.6%.
Conclusions:
- Adenosine treatment during CABS is safe and well-tolerated.
- Adenosine may be associated with a reduction in postoperative complications.
- Further research may confirm adenosine's role in improving outcomes in cardiac surgery.