Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy.

OBJECTIVE: Ischemic heart failure is an increasingly prevalent global health concern with major morbidity and mortality. Currently, therapies are limited, and novel revascularization methods might have a role. This study examined enhancing endogenous myocardial revascularization by expanding bone marrow-derived endothelial progenitor cells with the marrow stimulant granulocyte-monocyte colony-stimulating factor and recruiting the endothelial progenitor cells with intramyocardial administration of the potent endothelial progenitor cell chemokine stromal cell-derived factor. METHODS: Ischemic cardiomyopathy was induced in Lewis rats (n = 40) through left anterior descending coronary artery ligation. After 3 weeks, animals were randomized into 4 groups: saline control, granulocyte-monocyte colony-stimulating factor only (GM-CSF only), stromal cell-derived factor only (SDF only), and combined stromal cell-derived factor/granulocyte-monocyte colony-stimulating factor (SDF/GM-CSF) (n = 10 each). After another 3 weeks, hearts were analyzed for endothelial progenitor cell density by endothelial progenitor cell marker colocalization immunohistochemistry, vasculogenesis by von Willebrand immunohistochemistry, ventricular geometry by hematoxylin-and-eosin microscopy, and in vivo myocardial function with an intracavitary pressure-volume conductance microcatheter. RESULTS: The saline control, GM-CSF only, and SDF only groups were equivalent. Compared with the saline control group, animals in the SDF/GM-CSF group exhibited increased endothelial progenitor cell density (21.7 +/- 3.2 vs 9.6 +/- 3.1 CD34 + /vascular endothelial growth factor receptor 2-positive cells per high-power field, P = .01). There was enhanced vascularity (44.1 +/- 5.5 versus 23.8 +/- 2.2 von Willebrand factor-positive vessels per high-power field, P = .007). SDF/GM-CSF group animals experienced less adverse ventricular remodeling, as manifested by less cavitary dilatation (9.8 +/- 0.1 mm vs 10.1 +/- 0.1 mm [control], P = .04) and increased border-zone wall thickness (1.78 +/- 0.19 vs 1.41 +/- 0.16 mm [control], P = .03). (SDF/GM-CSF group animals had improved cardiac function compared with animals in the saline control group (maximum pressure: 93.9 +/- 3.2 vs 71.7 +/- 3.1 mm Hg, P < .001; maximum dP/dt: 3513 +/- 303 vs 2602 +/- 201 mm Hg/s, P < .05; cardiac output: 21.3 +/- 2.7 vs 13.3 +/- 1.3 mL/min, P < .01; end-systolic pressure-volume relationship slope: 1.7 +/- 0.4 vs 0.5 +/- 0.2 mm Hg/microL, P < .01.) CONCLUSION: This novel revascularization strategy of bone marrow stimulation and intramyocardial delivery of the endothelial progenitor cell chemokine stromal cell-derived factor yielded significantly enhanced myocardial endothelial progenitor cell density, vasculogenesis, geometric preservation, and contractility in a model of ischemic cardiomyopathy.

Active thermoregulation improves outcome of off-pump coronary artery bypass.

During off-pump coronary artery bypass grafting, hypothermia increases vasoconstriction, myocardial afterload, coagulopathy and postoperative bleeding. Traditional thermoregulatory techniques do not maintain core body temperature intraoperatively. The efficacy of a commercially available, computer-controlled, water-circulating, dorsal surface, active warming system for thermoregulatory control was evaluated. All patients who underwent non-emergency off-pump coronary bypass grafting by a single surgeon in a 1-year period were studied: the thermoregulation device was used in 50 cases and unavailable for use in 19. The patients who underwent active thermoregulation demonstrated significantly improved core body temperatures compared to the controls: lowest intraoperative, 35.8 degrees C +/- 0.1 degrees C vs. 35.0 degrees C +/- 0.2 degrees C; immediately postoperative, 36.5 degrees C +/- 0.1 degrees C vs. 35.6 degrees C +/- 0.2 degrees C; and 1-hour postoperative, 36.6 degrees C +/- 0.1 degrees C vs. 35.9 degrees C +/- 0.2 degrees C. Thermoregulated patients had significantly reduced 24-hour chest tube drainage (764 +/- 38 vs. 1227 +/- 183 mL), packed red blood cell transfusions (1.4 +/- 0.2 vs. 3.3 +/- 0.7 units), time to extubation (6.8 +/- 0.5 vs. 11.4 +/- 2.3 hours), intensive care unit stay (1.3 +/- 0.1 vs. 2.0 +/- 0.3 days), and hospital stay (4.3 +/- 0.1 vs. 5.1 +/- 0.3 days).

Should Standard On-Pump Protamine Dosing Formulas Be Recalculated for Off-Pump Coronary Artery Bypass Grafting?

Abstract Background: Since 1994 at the authors' institution, approximately 9000 cardiac surgical procedures were performed using activated clotting time (ACT)-monitored heparin anticoagulation for cardiopulmonary bypass and protamine administration calculated from a standard unchanged formula. This formula incorporates physiologic consequences of bypass pump-induced dilutional coagulopathy, platelet dysfunction, and coagulation/fibrinolytic cascade component activation, and thus may overcorrect in a subset of off-pump coronary artery bypass graft (OPCAB) patients who may in fact manifest a relative perioperative hypercoagulability state. This study evaluated a strategy of decreased protamine dosing in OPCAB. Methods: Eighty consecutive OPCAB patients who underwent surgery performed by a single surgeon at a single institution over a 12-month period were retrospectively analyzed. Patients underwent a mean of 2.91 +/- 0.1 OPCAB grafts with full heparinization and 50% of the calculated protamine dose was administered. ACT, partial thromboplastin times, thoracostomy tube outputs, transfusions, and clinical outcomes were assessed. Results: Of 80 patients, 76 (95%) returned to baseline ACT values with 50% protamine dosing. All patients demonstrated intraoperative clinical evidence of hemostasis. Mean 8- and 24-hour thoracostomy tube outputs were 424 +/- 24 mL and 806 +/- 38 mL, respectively. A mean of 1.7 +/- 0.2 packed red blood cell transfusions/patient was administered. There were no transfusions of platelets, fresh frozen plasma, or cryoprecipitate; no reexplorations; and no mortalities. Patients were discharged a mean of 4.4 +/- 0.1 days postoperatively. Conclusion: A standard protamine dosing formula adequate for on-pump cardiac surgical procedures significantly overestimates protamine requirements for OPCAB. Patients treated with decreased protamine do not appear to have adverse outcomes.

Off-pump revascularization for significant left ventricular dysfunction.

Left ventricular dysfunction is a predictor of perioperative morbidity and mortality in on-pump coronary artery bypass grafting. Obligatory global myocardial ischemia and injury induced during crossclamping as well as adverse systemic effects of cardiopulmonary bypass may induce a disproportionately greater overall physiologic insult in patients with poor ventricular function. All patients undergoing nonemergency off-pump coronary artery bypass by a single surgeon during an 18-month period were retrospectively analyzed. Two groups with preoperative ejection fraction classified as poor (10%-35%; n = 31) or normal (55%-80%; n = 60) were compared. The mean ejection fractions were 26% +/- 1% and 63% +/- 1% respectively, p < 0.000001. In those with significant left ventricular dysfunction, there were 2.8 +/- 0.1 grafts per patient, time to extubation was 8.4 +/- 1.2 hours, and discharge was after 4.9 +/- 0.6 days. These results were statistically equivalent to those in the group with normal left ventricular function. There was no intraaortic balloon pump insertion or mortality in either group. This technique provides an effective means of safely revascularizing patients with significant left ventricular dysfunction, and it may provide a valuable alternative approach in patients with ischemic cardiomyopathy.

Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction.

BACKGROUND: Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia. METHODS: Male Wistar rats, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min of ischemia and assayed for ATP levels. RESULTS: Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/s; p<0.0028), ejection fraction (29.1+/-1.7% versus 20.4+/-1.4%; p<0.0017), and preload adjusted maximal power (59.3+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/g ischemic tissue; p<0.0369). CONCLUSIONS: The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.

Robotic resection of an aortic valve papillary fibroelastoma.

Robotic technology has been applied to multiple cardiac surgical procedures. Purported benefits include decreased tissue trauma, reduced postoperative bleeding, fewer blood product transfusions, and shorter lengths of stay. We describe the case of a 50-year-old man with an incidentally discovered 1-cm mobile mass on the edge of the aortic valve noncoronary leaflet. The patient underwent robotic minimally invasive resection. The pathologic examination revealed papillary fibroelastoma.

Ethyl pyruvate enhances ATP levels, reduces oxidative stress and preserves cardiac function in a rat model of off-pump coronary bypass.

BACKGROUND: Off-pump coronary artery bypass grafting is associated with transient periods of myocardial ischemia during revascularization resulting in myocardial contractile dysfunction and oxidative injury. The purpose of this study was to investigate the efficacy of ethyl pyruvate as a myocardial protective agent in a rat model of off-pump coronary artery bypass grafting associated with transient myocardial dysfunction without infarction. METHODS: Wistar rats were subjected to transient ischemia via 10 min occlusion of the LAD coronary artery followed by 10 min of reperfusion. Animals received an IV bolus of Ringer's solution as a control (n=10) or Ringer's ethyl pyruvate (n=10) immediately before the initiation of ischemia and reperfusion. Myocardial ATP and lipid peroxidation levels were quantified for an estimation of energetics and oxidative stress, respectively. In vivo cardiac function was assessed throughout the ischemia and reperfusion periods. RESULTS: Ethyl pyruvate significantly increased myocardial ATP levels compared to controls (2650+/-759 nmol/g versus 892+/-276 nmol/g, p=0.04). Myocardial oxidative stress was significantly reduced in animals treated with ethyl pyruvate compared to controls (70.4+/-2.6 nmol/g versus 81.8+/-2.4 nmol/g, p=0.04). dP/dt max and cardiac output were significantly greater in the ethyl pyruvate group compared to controls during ischemia and reperfusion. CONCLUSIONS: Ethyl pyruvate enhances myocardial ATP levels, reduces oxidative stress, and preserves myocardial function in a model of transient ischemia/reperfusion injury not subject to myocardial infarction.