Differences in myocardial and peripheral VEGF and KDR levels after acute ischemia.

BACKGROUND: Recent clinical use of vascular endothelial growth factor (VEGF) in the treatment of both myocardial and peripheral ischemia has suggested the possibility of tissue specific coregulation of VEGF and its receptors (eg, kinase domain region [KDR]). The present study was performed to detect the relationship between VEGF and KDR protein levels after acute myocardial and peripheral ischemia. METHODS: Eleven dogs were divided into two groups: peripheral ischemia (n = 6, ligation of major limb arteries) and myocardial ischemia (n = 5, circumflex artery ligation). Muscle biopsy specimens were taken from the perfusion territories of the occluded circumflex artery and limb arteries 3 hours and 6 hours after ligation. Protein levels were determined using Western blot analysis. RESULTS: In myocardium, VEGF levels increased on average eightfold from baseline (p < 0.05) both 3 hours and 6 hours after occlusion, whereas myocardial KDR levels dropped by about 60% at 3 hours and 80% at 6 hours (p < 0.05). With limb ischemia, both VEGF and KDR levels were significantly elevated at 3 hours. CONCLUSIONS: In acute ischemia, regulation of VEGF and KDR may be controlled differently in cardiac and skeletal muscle. Myocardial KDR levels showed a significant decrease from baseline compared with a significant rise with peripheral ischemia.

Myocardial revascularization in the elderly using beating heart coronary artery bypass surgery.

BACKGROUND: Beating heart or "off-pump" coronary artery bypass (OP-CAB) has become an accepted method of myocardial revascularization by reducing the perioperative morbidity related to cardiopulmonary bypass (CPB). However, the efficacy of OP-CAB has not been well established in the elderly patient population. METHODS: OP-CABs were performed in 53 patients aged 75 years and older, at Pitt County Memorial Hospital from January 1996 to October 1999, either through a median sternotomy or an anterior thoracotomy. These results were compared with 220 patients who underwent standard coronary artery bypass graft (CABG) operation using CPB during the same time period. RESULTS: Mean patient age for both groups was 79+/-0.5 years and preoperative risk factors were similar. There were no differences in postoperative myocardial infarction, atrial fibrillation, bleeding, neurologic complications, or renal failure. There were no deaths after OP-CAB, compared with the 7.6% operative mortality rate after CABG (p<0.05). The OP-CAB group had a significantly shorter postoperative length of stay (4.4+/-0.4 days vs. 8.4+/-0.6 days) and lower transfusion requirements (0.4+/-0.1 units packed red blood cells vs 1.9+/-0.2 units packed red blood cells) than the CABG group. CONCLUSIONS: Our data demonstrate that OP-CAB is a safe and efficacious method of myocardial revascularization in the elderly, and may actually be preferential in these patients when applicable.

Minimally invasive cardiac operation: adapting cardioprotective strategies.

BACKGROUND: Minimally invasive heart operation differs from traditional cardiac operations through the omission of a sternotomy, cardiopulmonary bypass, or both. Current concerns with minimally invasive operation include: operative safety, learning curve, operative times, arrest times, and adequacy of myocardial protection. While many of the protective strategies used for traditional procedures may be applied to minimally invasive cardiac operations, the safe applications of minimally invasive operations require unique techniques of myocardial protection. METHODS AND RESULTS: Omission of extracorporeal perfusion may benefit patients through attenuation of systemic inflammatory response, decrement in neurologic insults, and reduced bleeding complications. As a counterbalance, surgeons must consider long-term operative quality and level of myocardial protection provided during beating heart coronary operation. Current issues that must be addressed include: pharmacologic management, coronary collateralization and ischemic preconditioning, the utility of intraluminal coronary shunts, and technical adequacy of the anastomosis. Nonsternotomy cardiopulmonary bypass methods utilize alternative incisions and "port-access" technology, and may render more rapid patient recovery including: decreased pain, shortened hospital stay, and more rapid return to work. Altered strategies of myocardial protection in a closed chest environment must address: method of cannulation, technique of aortic occlusion, rapidity and maintenance of cardiac arrest, and cardiac de-airing techniques. CONCLUSIONS: Previous obstacles to minimally invasive cardiac operations included limitations in operative exposure, inadequate perfusion technology, and inability to provide myocardial protection. Recent advances in videoscopic visualization and evolving mechanisms of myocardial protection may justify the expanding application of minimally invasive techniques.

Deleterious effects of cardiopulmonary bypass on early graft function after single lung allotransplantation: evaluation of a heparin-coated bypass circuit.

Clinical lung transplantation may necessitate the use of cardiopulmonary bypass during the procedure, resulting in increased morbidity with more severe early graft dysfunction and increased blood loss. A heparin surface-coated cardiopulmonary bypass circuit is now available with improved biocompatibility and reduced systemic heparin requirements and may offer advantages compared with standard uncoated cardiopulmonary bypass circuits. This study investigates in a canine model of single-lung allotransplantation whether cardiopulmonary bypass adversely affects early graft function and whether a heparin-coated cardiopulmonary bypass circuit with reduced systemic heparin dosage improves results compared with standard uncoated cardiopulmonary bypass systems. Fifteen dogs underwent left single-lung allotransplantation with occlusion of the contralateral pulmonary artery and bronchus 1 hour after reperfusion. In one group, five animals underwent the procedure without cardiopulmonary bypass. In the group with uncoated circuits, five animals underwent the procedure with the use of standard uncoated cardiopulmonary bypass circuits with full systemic heparin dosage. In the group with heparin-coated circuits, five animals underwent the procedure with the use of heparin-coated cardiopulmonary bypass circuits and reduced systemic heparin dosage. Early graft function was evaluated by arterial oxygenation, pulmonary mechanics, lung water measurements, and histologic analysis. Hemodynamics and postoperative blood loss were also measured. Two hours after reperfusion, partial pressure of oxygen in arterial blood on an inspired oxygen fraction = 1.0 was significantly greater (p < 0.001) in the group without cardiopulmonary bypass (467 +/- 58 mm Hg) than in the group with uncoated circuits (114 +/- 90 mm Hg) and the group with heparin-coated circuits (193 +/- 105 mm Hg), with no significant difference between the groups undergoing bypass procedures. Lung compliance decreased and lung water increased in all transplanted lungs without significant differences between groups. Histologic analysis did not differentiate between the groups. After reperfusion, cardiac index and mean arterial pressure were significantly reduced in the groups with uncoated circuits and with heparin-coated circuits compared with the group that did not undergo cardiopulmonary bypass (p < 0.001). Postoperative blood loss was significantly less (p < 0.002) in the group that did not undergo cardiopulmonary bypass (90 ml +/- 38 ml) compared with both the group with uncoated circuits (750 +/- 15 ml) and the group with heparin-coated circuits (690 +/- 387 ml), with no significant difference between the groups that underwent bypass. The use of cardiopulmonary bypass with systemic heparinization is detrimental to early graft function in this canine model of left single-lung allotransplantation.(ABSTRACT TRUNCATED AT 400 WORDS)

Improved survival following pediatric cardiac transplantation in high-risk patients.

BACKGROUND: Preoperative hemodynamic support, complex congenital heart disease, and elevated pulmonary vascular resistance present particular challenges for pediatric heart transplantation. This study was performed to identify preoperative factors that influence survival after pediatric heart transplantation over two eras of pediatric heart transplant experience. METHODS AND RESULTS: We retrospectively analyzed demographic, clinical, and hemodynamic data from 67 pediatric patients who underwent heart transplantation between February 1982 and June 1992 and compared survival between two eras (early experience versus late experience). During the early experience (group 1: February 1982 to August 1989), univariate analysis identified congenital heart disease, pretransplant extracorporeal membrane oxygenator (ECMO) support, inotropic and/or ventilatory support (UNOS status I), elevated transpulmonary gradient (at least 15 mm Hg), and elevated pulmonary vascular resistance index (at least 4 Wood units.m2) as preoperative risk factors for early death after pediatric heart transplantation. However, in the late experience (group 2: September 1989 to June 1992), the only risk factor for premature death by univariate analysis was elevated transpulmonary gradient. By multivariate analysis, elevated transpulmonary gradient was the only risk factor for our early, late, and entire experiences. One-year survival after transplantation for congenital heart disease was improved from 46% in group 1 to 73% in group 2 (P < .05). In group 1, only one patient (25%) with pretransplant ECMO support survived 1 year, whereas 66% (four of six) survived more than 1 year in group 2. CONCLUSIONS: Although elevated transpulmonary gradient continues to be a significant risk factor for pediatric heart transplantation, candidates with congenital heart disease, UNOS status I, and pretransplant ECMO support now can be successfully transplanted with reasonable hope for extended survival.

Aspects of lung transplantation that contribute to increased severity of pneumonia. An experimental study.

In lung or heart-lung transplant recipients, complications as a result of pulmonary infections continue to be the most frequent causes of morbidity and mortality. This study was undertaken to identify the contributions of (1) thoracotomy, (2) interruption of lymphatic vessels and bronchial arteries, (3) transplant procedure, (4) drug-induced immunosuppression, and (5) graft allogenicity to the increased risk of pneumonia in lung transplantation. Lewis rats were inoculated with 10(5) colony-forming units of Legionella pneumophila serogroup 1 by direct instillation into the trachea after one of the following: a general anesthetic with no operation; a left thoracotomy; a left thoracotomy with pulmonary hilar stripping; an isogeneic orthotopic left lung transplant with or without immunosuppression; or an allogeneic transplant with immunosuppression with Brown-Norway rats as donors. Immunosuppression was induced with an intramuscular injection of cyclosporine (25 mg/kg of body weight) from the inoculation day to day 3. All rats were killed on day 6, and severity of infection was determined by quantitative culture of Legionella organisms in the lungs and spleen, titer of Legionella urinary antigen, differential cell count in bronchoalveolar lavage fluid, body weight loss, and gross inspection of the lung. Significant increases in lung Legionella concentration occurred as a result of the addition of pulmonary hilar stripping (from 10(5.13 +/- 0.34) in the thoracotomy group to 10(5.66 +/- 0.25) in the thoracotomy with hilar stripping group, p = 0.013) and the addition of immunosuppression (from 10(5.47 +/- 0.47) in the isogeneic transplant group to 10(6.94 +/- 0.52) in the isogeneic transplant with immunosuppression group, p = 0.00016). Thoracotomy, transplant procedures, and allogenicity itself resulted in no significant increases. The results for all other indicators paralleled those for lung culture. We conclude that the combination of drug-induced immunosuppression with lung denervation and interruption of lymphatic vessels and bronchial arteries results in the early development and increased severity of pneumonia in lung transplantation.

Graft cytokine mRNA activity in rat single lung transplants by reverse transcription-polymerase chain reaction: effect of cyclosporine.

Intragraft levels of cytokine mRNA were studied in an orthotopic rat left lung transplant model. Three groups of rats were compared at 7 days after transplantation. Isogeneic (Lewis to Lewis), allogeneic (Brown-Norway to Lewis) untreated, and cyclosporine-treated (25 mg/kg/day, intramuscularly) allogeneic animals underwent analysis of cytokine mRNA isolated from total RNA in freshly excised grafts. Reverse transcription-polymerase chain reaction amplification of interleukin (IL)-2, IL-4, and actin (control) mRNA was performed with custom-synthesized oligonucleotide amplimers targeted to known sequences of rat IL-2 and IL-4 cDNA. Semiquantitative analysis was performed by radioanalytic scanning of gel preparations. Sample specimens from the retrieved grafts were also graded histologically for rejection on a five-point scale. Rejection was most severe in the untreated allografts (p < 0.003). IL-2 mRNA was significantly greater in the untreated allografts when compared with isografts (p < 0.05) and cyclosporine-treated allografts (p < 0.05). No significant differences in IL-4 mRNA between groups were observed. We conclude that semiquantitative analysis of cytokine mRNA by reverse transcription-polymerase chain reaction is a useful and sensitive method for the study of acute rejection in lung grafts and that this technique may become an important tool in future studies of cytokine-mediated responses in cyclosporine-treated allografts.

The accuracy and precision of an open-circuit system to measure oxygen consumption and carbon dioxide production in neonates.

We measured the oxygen consumption, carbon dioxide production, and respiratory quotient during the combustion of a known mass of anhydrous ethanol and methanol to assess the accuracy of an open-circuit flow-through system. Continuous measurements were made of the mass of alcohol burned, the velocity of gas flow through the apparatus, and simultaneous measurements of the fractional concentration of oxygen, carbon dioxide and nitrogen of the inlet and outlet gas using paramagnetic oxygen analyzer, infrared carbon dioxide meter, and mass spectrometer. Standard respiratory and stoichiometric equations were used to calculate the oxygen consumption, carbon dioxide production and RQ for the mass of absolute alcohol combustion per unit time. In a series of 12 consecutive laboratory experiments (on 7 days), the measured values of gas exchange (similar to the rate of respiratory gas exchange by an infant of 1-4 kg) were in agreement within 5% of the true values for ethanol and methanol combustion, confirming the validity of the open-circuit method. The paramagnetic oxygen analyzer and the mass spectrometer gave similar oxygen consumption results and differed very little when the rate of absolute alcohol combustion was used to quantify the accuracy of the complete measurement system. A positive measurement error was observed for the carbon dioxide production results from both the IR meter and mass spectrometer, with the result that the respiratory quotient measurements were 3.4-4.7% higher than the true value. The mass spectrometer gave more precise oxygen consumption results, whereas smaller variance of carbon dioxide production measurements was observed using the infrared CO2 meter.(ABSTRACT TRUNCATED AT 250 WORDS)