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Cardioprotective effects of acute isovolemic hemodilution in a rat model of transient coronary occlusion.Licker M, Mariethoz E, Costa MJ, Morel D. Crit Care Med 2005; 33:2302-2308.Reviewer: Michael H. Wall, MD
Abstract: The authors hypothesized that acute normovolemic isodilution (AIH) would have cardioprotective effects in acute coronary ischemia and infarction. Male Sprague-Dawley rats were anesthetized with isoflurane and fentanyl. The AIH group was hemodiluted to a target hematocrit of 28% using 6% hydroxyethyl starch in a 1:1 ratio over 10 minutes. The AIH (Hct 26%) and control groups (Hct 42%) underwent 30 minutes of acute occlusion of the left anterior descending (LAD) coronary artery. Flow was restored to the LAD, the animals emerged from anesthesia and followed for 48 hours before they were sacrificed. Fatal arrhythmias were less common in the AIH group than in the control group (13% vs 47%, p <0.05) and 48 hour survival was higher in the AIH group (83% vs 42%, p <0.05). Cardiac troponin release was significantly lower in the AIH group, and although the myocardial area-at-risk was the same in both groups, the myocardial infarct size was significantly smaller in the AIH group. There was no difference in myocardial neutrophil infiltration between groups. Because there were no differences in hemodynamics or neutrophil infiltration, the mechanism of myocardial protection was probably not due to a metabolic sparing or anti-inflammatory effect. The authors hypothesize that AIH may provide cardioprotection by several mechanisms including: 1) erythropoietin-triggered activation of receptors that inhibit apoptosis, 2) an AIH-induced increased collateral blood flow resulting in decreased infarct size despite similar area-at-risk in the AIH group, 3) improved myocardial blood flow in the presence of hemodilution, 4) improved red blood cell velocity and decreased blood viscosity; both improving microcirculatory oxygen delivery and, 5) possibly a lower systemic vascular resistance due to AIH, thus decreasing oxygen requirements. The authors point out that these findings of single coronary occlusion may not be applicable to patients with chronic diffuse multivessel coronary artery disease and chronic endothelial disfunction. However, these findings are consistent with a study of pre-bypass AIH (to Hct of 28%) in humans that showed fewer arrhythmias, lower release of biomarkers and lower inotrope requirements in the AIH group.1 Comments: The "transfusion trigger" in patients with coronary artery disease or undergoing cardiac surgery is controversial. However, it is known that there are risks associated with transfusion including immunosuppression, bacterial and viral infection and transfusion-related acute lung injury. It has clearly been shown that there is no difference in outcomes between a liberal (Hb 10-12 g/dL) vs restrictive (Hb 7-9 g/dL) transfusion strategy in critically ill patients or a sub-group of critically ill patients with coronary artery disease.2 However, studies of Jehovah's Witness patients with coronary artery disease have shown an association with increased mortality with a Hb < 8 g/dL.3 Also, the authors of this paper found that AIH in a Hct of 25% (Hb 8.3 g/dL) resulted in unstable hemodynamics and bleeding complications. Two recent large retrospective studies have shown different results regarding transfusion in patients with acute myocardial infarction. One showed an association with improved outcome with a transfusion trigger of < 11 gm/dL.4 The other showed no impact of transfusion with a trigger between 7-8 gm/dL, but a worse outcome was associated with a trigger of > 10 gm/dL.4,5 This paper also emphasizes the anti-apoptotic role of erythropoietin in ischemia and reperfusion. More studies of erythropoietin, evaluating its effects on other organ systems, need to be done in critically ill patients and patients undergoing cardiac surgery. Finally, the authors used 6% hydroxyethyl starch for AIH. Studies on other fluids should also be done to determine if 6% hydroxyethyl starch is the optimum fluid for AIH. There is growing evidence that a Hb of 8-10 g/dL is safe in normovolemic patients with coronary artery disease without acute coronary syndromes. Further animal and clinical trials will need to be done to determine the optimal Hb in patients with coronary artery disease and acute coronary syndromes and to determine the optimum Hb before, during, and after cardiac surgery. It may be lower than we think! References
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