Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: role of K+ channels.

This study was designed to identify mechanisms responsible for coronary vasodilation in response to progressive decreases in hematocrit. Isovolemic hemodilution was produced in open-chest, anesthetized swine via concurrent removal of 500 ml of arterial blood and the addition of 500 ml of 37 °C saline or synthetic plasma expander (Hespan, 6% hetastarch in 0.9% sodium chloride). Progressive hemodilution with Hespan resulted in an increase in coronary flow from 0.39 ± 0.05 to 1.63 ± 0.16 ml/min/g (P < 0.001) as hematocrit was reduced from 32 ± 1 to 10 ± 1% (P < 0.001). Overall, coronary flow corresponded with the level of myocardial oxygen consumption, was dependent on arterial pressures ≥ ~ 60 mmHg, and occurred with little/no change in coronary venous PO2. Anemic coronary vasodilation was unaffected by the inhibition of nitric oxide synthase (L-NAME: 25 mg/kg iv; P = 0.92) or voltage-dependent K+ (K V) channels (4-aminopyridine: 0.3 mg/kg iv; P = 0.52). However, administration of the K ATP channel antagonist (glibenclamide: 3.6 mg/kg iv) resulted in an ~ 40% decrease in coronary blood flow (P < 0.001) as hematocrit was reduced to ~ 10%. These reductions in coronary blood flow corresponded with significant reductions in myocardial oxygen delivery at baseline and throughout isovolemic anemia (P < 0.001). These data indicate that vasodilator factors produced in response to isovolemic hemodilution converge on vascular smooth muscle glibenclamide-sensitive (K ATP) channels to maintain myocardial oxygen delivery and that this response is not dependent on endothelial-derived nitric oxide production or pathways that mediate dilation via K V channels.

iPSC-Derived Vascular Cell Spheroids as Building Blocks for Scaffold-Free Biofabrication.

Recently a protocol is established to obtain large quantities of human induced pluripotent stem cells (iPSC)-derived endothelial progenitors, called endothelial colony forming cells (ECFC), and of candidate smooth-muscle forming cells (SMFC). Here, the suitability for assembling in spheroids, and in larger 3D cell constructs is tested. iPSC-derived ECFC and SMFC are labeled with tdTomato and eGFP, respectively. Spheroids are formed in ultra-low adhesive wells, and their dynamic proprieties are studied by time-lapse microscopy, or by confocal microscopy. Spheroids are also tested for fusion ability either in the wells, or assembled on the Regenova 3D bioprinter which laces them in stainless steel micro-needles (the "Kenzan" method). It is found that both ECFC and SMFC formed spheroids in about 24 h. Fluorescence monitoring indicated a continuous compaction of ECFC spheroids, but stabilization in those prepared from SMFC. In mixed spheroids, the cell distribution changed continuously, with ECFC relocating to the core, and showing pre-vascular organization. All spheroids have the ability of in-well fusion, but only those containing SMFC are robust enough to sustain assembling in tubular structures. In these constructs a layered distribution of alpha smooth muscle actin-positive cells and extracellular matrix deposition is found. In conclusion, iPSC-derived vascular cell spheroids represent a promising new cellular material for scaffold-free biofabrication.

Preoperative Aspirin Use and Its Effect on Adverse Events in Patients Undergoing Cardiac Operations.

BACKGROUND: Preoperative aspirin use within 5 days of cardiac operations is controversial. Aspirin could reduce cardiovascular complications and yet might increase risk of bleeding. Recent reports showed conflicting results, and whether aspirin has variable effects for different cardiac surgical procedures is unclear. METHODS: A single-center retrospective cohort analysis was performed. After propensity score matching (PSM) for identified confounders, the relationship between preoperative aspirin use and 30-day all-cause mortality, postoperative renal failure, major adverse cardiocerebral events (MACE), blood transfusion, reoperation for bleeding, and postoperative infection were estimated with separate logistic regression models. RESULTS: Preoperative aspirin therapy was associated with a 49% (p = 0.04) increased risk of reoperation for bleeding among 868 matched pairs of patients undergoing valve operations. Among 725 matched patients undergoing coronary artery bypass grafting (CABG), preoperative aspirin therapy was not associated with a statistically significant higher risk of reoperation for bleeding. However, preoperative aspirin use, compared with nonuse, was not associated with risks of MACE, 30-day mortality, postoperative renal failure, blood transfusion, or postoperative infection in the entire cohort, in patients undergoing valve operations only, and in patients undergoing CABG only after PSM. CONCLUSIONS: Preoperative aspirin use in all patients undergoing cardiac operations was not associated with risks of major cardiac, cerebral, or renal complications and infections and death; however, the risk of reoperation for bleeding was elevated among preoperative aspirin users compared with nonusers in a subpopulation of patients undergoing valve operations only.