Cell- and gene therapy for ischemic heart disease.

Despite advances in pharmacological therapies, cardiovascular surgery, use of mechanical assist devices, and organ transplantation, more than half of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The use of cellular cardiomyoplasty and gene therapy offer a promising approach for both the prevention and treatment of heart failure. This review will discuss the current state of these emerging fields and the prospects of introducing the methods into clinical practice. Since functional restoration of the damaged heart presents a formidable challenge, developing strategies for the prevention of post-infarct heart failure remains of utmost priority. New strategies to optimize cell delivery, homing and survival on the one side and safe and efficient application of gene therapy to the failing myocardium on the other side are indispensable in order to achieve myocardial recovery after acute infarction or chronic ischemic damage.

Ongoing procedure development in robotically assisted totally endoscopic coronary artery bypass grafting (TECAB).

BACKGROUND: Totally endoscopic coronary artery bypass grafting (TECAB) using robotics requires stepwise introduction into a heart surgery program. It is the aim of this study to evaluate the state of procedure development after continued application of telemanipulation techniques in the clinical setting. We also sought to assess perioperative and intermediate term clinical results after robotically assisted CABG. PATIENTS AND METHODS: From June 2001 to March 2005, robotically assisted CABG using the daVinci system was carried out in 107 patients with single and multi-vessel coronary artery disease. The following procedures were performed: robotically assisted endoscopic left internal mammary artery (LIMA) harvesting and completion of the procedure as conventional CABG, MIDCAB, or OPCAB (n = 22), robotically assisted suturing of LIMA-to-LAD anastomoses during conventional CABG (n = 28), TECAB on the arrested heart using remote access perfusion (n = 48), TECAB on the beating heart using an endostabilizer (n = 8), takedown of adhesions (TECAB intended) (n = 1). RESULTS: Hospital mortality was 0% and cumulative risk adjusted mortality reached 1.6 lives saved versus EuroSCORE predictions. Undesirable surgical events (USE) such as conversion, on table revision, or postoperative revision procedures occurred in 34 out of 107 (32%) patients. Median ventilation time and ICU stay, however, were 11(0-278) hours and 21(11-389) hours, respectively. Cumulative 3 years survival was 100% and freedom from angina at 3 years was 97%. CONCLUSIONS: We conclude that despite being surgically challenging robotically assisted coronary artery surgery can be implemented with acceptable safety. TECAB procedures have reached a reproducible state. Perioperative mortality after robotically assisted CABG may be lower than predicted. Intermediate term clinical results are very satisfactory.

Robotic totally endoscopic coronary artery bypass: program development and learning curve issues.

BACKGROUND: The introduction of new procedures in heart surgery is a critical phase that includes learning curves and the risk of increased mortality or morbidity. Totally endoscopic coronary artery bypass grafting using robotic techniques represents such an innovative procedure. The aim of this report is to demonstrate the safe introduction of totally endoscopic coronary artery bypass grafting using a stepwise and modular approach. METHODS: From June 2001 until December 2002, 50 procedures were performed using the da Vinci telemanipulator system. After baseline training the following procedure modules were carried out in a stepwise manner: robotically assisted endoscopic left internal thoracic artery harvesting and completion of the procedure as conventional coronary artery bypass grafting, minimally invasive direct coronary artery bypass, or off-pump coronary artery bypass (n = 19), robotically assisted suturing of left internal thoracic artery to left anterior descending anastomoses during conventional coronary artery bypass grafting (n = 15), totally endoscopic coronary artery bypass grafting on the arrested heart using remote access perfusion and aortic endocclusion coronary bypass grafting (n = 15). One patient was excluded intraoperatively from a robotic procedure due to pleural adhesions. RESULTS: A significant learning curve was observed for left internal thoracic artery takedown time, y(min) = 181 - 39 x ln(x) (x = procedure number) (P <.001), and total operative time in totally endoscopic coronary artery bypass grafting, y(min) = 595 - 87 x ln(x) x = (procedure number) (P =.028). The conversion rate in totally endoscopic coronary artery bypass grafting was 2/15. Intensive care unit stay correlated significantly with total operative time (r =.427, P =.002). There was no hospital mortality. CONCLUSION: Totally endoscopic coronary artery bypass grafting can be safely implemented into a heart surgery program. Learning curves are steep for robotic left internal thoracic artery takedown and for performance of totally endoscopic coronary artery bypass grafting. Long operative times translate into prolonged intensive care unit stay in specific cases but not into increased mortality.

Diltiazem during reperfusion preserves high energy phosphates by protection of mitochondrial integrity.

OBJECTIVE: This study evaluates the effects of diltiazem administered during reperfusion on hemodynamic, metabolic, and ultrastructural postischemic outcome. METHODS: Hearts of 38 adult White New Zealand rabbits underwent 60 min of global cold ischemia followed by 40 min of reperfusion in an erythrocyte perfused isolated working heart model. Hearts were randomly assigned to four groups and received diltiazem (0.1, 0.25, and 0.5 micromol/l) during reperfusion only, or served as control. RESULTS: The postischemic time courses of heart rate, aortic flow, and external stroke work clearly reflected the dose-dependent negative chronotropic and inotropic efficacy of diltiazem in the two higher concentrations. High energy phosphates (HEP) determined from myocardial biopsies taken after 40 min of reperfusion were significantly better preserved in all treatment groups compared to control hearts. Similarly ultrastructural grading of mitochondria and myofilaments revealed a significant reduction of reperfusion injury in hearts that received diltiazem compared to control. CONCLUSIONS: Diltiazem protects mitochondrial integrity and function, thereby preserving myocardial HEP levels. Only low dose diltiazem (0.1 micromol/l) during reperfusion combines both, optimal mitochondrial preservation with minimal changes in hemodynamics.