American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2010
Randomized Controlled TrialCardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure.
The incretin hormone glucagon-like peptide-1 (GLP-1) and its analogs are currently emerging as antidiabetic medications. GLP-1 improves left ventricular ejection fraction (LVEF) in dogs with heart failure (HF) and in patients with acute myocardial infarction. We studied metabolic and cardiovascular effects of 48-h GLP-1 infusions in patients with congestive HF. ⋯ GLP-1 infusion increased circulating insulin levels and reduced plasma glucose concentration but had no major cardiovascular effects in patients without diabetes but with compensated HF. The impact of minor increases in heart rate and diastolic blood pressure during GLP-1 infusion requires further studies. Hypoglycemia was frequent and calls for caution in patients without diabetes but with HF.
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2010
Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins.
Hemoglobin (Hb)-based O(2) carriers (HBOCs) constitute a class of therapeutic agents designed to correct the O(2) deficit under conditions of anemia and traumatic blood loss. The O(2) transport capacity of ultrahigh-molecular-weight bovine Hb polymers (PolybHb), polymerized in the tense (T) state and relaxed (R) state, were investigated in the hamster chamber window model using microvascular measurements to determine O(2) delivery during extreme anemia. The anemic state was induced by hemodilution with a plasma expander (70-kDa dextran). ⋯ The increased tissue Po(2) attained with T-state PolybHb results from the larger amount of O(2) released from the PolybHb and maintenance of macrovascular and microvascular hemodynamics compared with R-state PolybHb. These results suggest that the extreme high O(2) affinity of R-state PolybHb prevented O(2) bound to PolybHb from been used by the tissues. The results presented here show that T-state PolybHb, a high-viscosity O(2) carrier, is a quintessential example of an appropriately engineered O(2) carrying solution, which preserves vascular mechanical stimuli (shear stress) lost during anemic conditions and reinstates oxygenation, without the hypertensive or vasoconstriction responses observed in previous generations of HBOCs.
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2010
TLR2 ligands attenuate cardiac dysfunction in polymicrobial sepsis via a phosphoinositide 3-kinase-dependent mechanism.
Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. In the present study, we examined the effect of Toll-like receptor 2 (TLR2) ligands, peptidoglycan (PGN), and Pam3CSK4 (Pam3) on cardiac function in cecal ligation and puncture (CLP)-induced sepsis in mice. We also investigated whether the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is involved in the effect of TLR2 ligands on cardiac function in CLP mice. ⋯ PI3K inhibition abolished the PGN-induced attenuation of cardiac dysfunction in CLP mice. In conclusion, these data demonstrate that the administration of TLR2 ligands, PGN, or Pam3 attenuates cardiac dysfunction in septic mice via a TLR2/PI3K-dependent mechanism. More significantly, Pam3 therapeutic treatment will have a potential clinical relevance.
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2010
Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs.
Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. ⋯ The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37 degrees C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis.