Todd J. Grand

Placental Growth Factor Provides a Novel Local Angiogenic Therapy for Ischemic Cardiomyopathy

Abstract  Background: Heart failure occurs predominantly due to coronary artery disease and may be amenable to novel revascularization therapies. This study evaluated the effects of placental growth factor (PlGF), a potent angiogenic agent, in a rat model of ischemic cardiomyopathy. Methods: Wistar rats underwent high proximal ligation of the left anterior descending coronary artery and direct injection of PlGF (n = 10) or saline as a control (n = 10) into the myocardium bordering the ischemic area. After 2 weeks, the following parameters were evaluated: ventricular function with an aortic flow probe and a pressure/volume conductance catheter, left ventricular (LV) geometry by histology, and angiogenesis by immunofluorescence. Results: PlGF animals had increased angiogenesis compared to controls (22.8 ± 3.5 vs. 12.4 ± 3.2 endothelial cells/high‐powered field, p < 0.03). PlGF animals had less ventricular cavity dilation (LV diameter 8.4 ± 0.2 vs. 9.2 ± 0.2 mm, p < 0.03) and increased border zone wall thickness (1.85 ± 0.1 vs. 1.38 ± 0.2 mm, p < 0.03). PlGF animals had improved cardiac function as measured by maximum LV pressure (95.7 ± 4 vs. 73.7 ± 2 mmHg, p = 0.001), maximum dP/dt (4206 ± 362 vs. 2978 ± 236 mmHg/sec, p = 0.007), and ejection fraction (25.7 ± 2 vs. 18.6 ± 1%, p = 0.02). Conclusions: Intramyocardial delivery of PlGF following a large myocardial infarction enhanced border zone angiogenesis, attenuated adverse ventricular remodeling, and preserved cardiac function. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.

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°C ± 0.1°C vs. 35.0°C ± 0.2°C; immediately postoperative, 36.5°C ± 0.1°C vs. 35.6°C ± 0.2°C; and 1-hour postoperative, 36.6°C ± 0.1°C vs. 35.9°C ± 0.2°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).

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.