Excimer versus carbon dioxide transmyocardial laser revascularization: effects on regional left ventricular function and perfusion.

BACKGROUND: Transmyocardial laser revascularization (TMR) has been established with the carbon dioxide (CO2) laser. The largely unstudied excimer laser creates channels through chemical bond dissociation instead of thermal ablation, thereby avoiding thermal injury. We sought to compare the effects of CO2 and excimer TMR in a porcine model of chronic ischemia. METHODS: Pigs underwent ameroid constrictor placement on the circumflex artery to create chronic ischemia. TMR was performed with CO2 (n = 8) or excimer (n = 8) laser 6 weeks later; controls (n = 7) had ameroid placement only. Regional myocardial blood flow (RMBF), determined by radioactive microspheres, and regional myocardial function, determined by percent segmental shortening (%SS), were assessed 18 weeks after ameroid placement. RESULTS: Values are mean +/- SD. In the ischemic zone, RMBF (mL/min/g) was improved in the CO2 (0.73 +/- 0.19) and excimer (0.78 +/- 0.22) groups when compared with controls (0.55% +/- 0.12%, p < 0.05). %SS was also improved in the CO2 (15.2% +/- 5.5%) and excimer (15.3% +/- 5.1%) groups when compared with controls (8.0% +/- 4.2%, p < 0.05). CONCLUSIONS: Excimer and CO2 TMR significantly improve RMBF and regional function in this porcine model of chronic myocardial ischemia despite fundamentally different tissue interactions.

LV-powered coronary sinus retroperfusion reduces infarct size in acutely ischemic pigs.

BACKGROUND: We developed a prosthetic left ventricle (LV) to coronary sinus (CS) shunt (LVCSS) that is autoregulating and provides LV-powered retrograde perfusion of the coronary sinus. METHODS: Each of 20 Yorkshire pigs underwent 1 hour of left anterior descending diagonal artery occlusion followed by 3 hours of reperfusion. The controls (n = 5) did not have shunt treatment. The LVCSS group (n = 9) underwent shunt treatment during the ischemic period. The LVCSS with partial coronary sinus occlusion (PCSO) group (LVCSS+PCSO, n = 6) underwent shunt treatment and PCSO during the ischemic period. Vital staining and planimetry techniques were used to determine the area at risk for infarction and the area of necrosis. RESULTS: The area at risk was not significantly different among groups. The area of necrosis was decreased by 53% in the LVCSS group and by 73% in the LVCSS+PCSO group when compared to controls (p<0.01 among all groups). CONCLUSIONS: The LVCSS reduces infarct size in pigs after acute coronary artery occlusion. The addition of PCSO to LVCSS further improves myocardial salvage.

Combination TMR and gene therapy.

Transmyocardial laser revascularization is a promising surgical technique that relieves angina and improves subendocardial perfusion in patients with chronic ischemic heart disease refractory to medical management and not amenable to conventional revascularization techniques. We detail our laboratory experience at the Brigham and Women's Hospital with transmyocardial laser revascularization and discuss the potential clinical applications of this work.

Complete reversal of ischemic wall motion abnormalities by combined use of gene therapy with transmyocardial laser revascularization.

INTRODUCTION: Transmyocardial laser revascularization is believed to induce an angiogenic response within ischemic myocardium. We evaluated transgene expression in the setting of transmyocardial laser revascularization and hypothesized that intramyocardial injection of plasmid DNA encoding the gene for vascular endothelial growth factor could enhance the revascularization achieved by transmyocardial laser revascularization, resulting in improved cardiac function. METHODS: Ten Yorkshire pigs had carbon dioxide-transmyocardial laser revascularization or acupuncture sites with injections of an expression plasmid encoding the gene for beta-galactosidase with or without HVJ-liposomes. Three days after transduction, transgene expression was determined by enzyme-linked immunosorbent assay. Six weeks after placement of a constrictor on the left circumflex artery, 29 pigs were randomized to ischemic controls (n = 5), transmyocardial laser revascularization (n = 4), transmyocardial laser revascularization with expression plasmid beta-galactosidase injections (n = 5), expression plasmid-vascular endothelial growth factor injections (n = 4), or transmyocardial laser revascularization with expression plasmid-vascular endothelial growth factor (n = 5) and harvested 6 weeks after therapy. Six transmyocardial laser revascularization pigs had either expression plasmid beta-galactosidase or expression plasmid-vascular endothelial growth factor injections and were harvested at 2 weeks. Normal pigs (n = 5) were included for comparison. Left ventricular free wall motion was assessed by a cardiologist in a blinded manner. RESULTS: Transgene expression did not vary significantly with or without HVJ-liposomes in transfected transmyocardial laser revascularization myocardium. However, expression was detected in 56 of 60 (93%) transmyocardial laser revascularization-transfected sites, but in only 10 of 20 (50%) non-transmyocardial laser revascularization sites (P < .001). All (5 of 5 hearts) of the transmyocardial laser revascularization-vascular endothelial growth factor treated hearts displayed no evidence of wall motion abnormalities. Only these hearts had a statistically significantly different rate of wall motion abnormality compared with ischemic controls (P = .004). CONCLUSION: Transfection efficiency was improved with the use of transmyocardial laser revascularization. Wall motion abnormalities were completely reversed within 6 weeks after transmyocardial laser revascularization with the direct injection of an expression plasmid encoding vascular endothelial growth factor.

Acute pancreatitis caused by penicillin.

Acute pancreatitis in childhood is a rare condition but should still be considered in all children presenting with abdominal pain. A complete history and physical exam with emphasis on recent trauma, infection, chronic diseases, and current medications should be obtained. Numerous and varied drugs have been implicated in the development of pancreatitis. Since many of these drugs are among most physicians' armamentarium, it is important to establish their causal relationship to pancreatitis. Careful appraisal of the drugs associated with acute pancreatitis and of the primary disease for which they were prescribed may, in the long run, provide new avenues of thought as to the pathogenesis of drug-induced pancreatitis.

Innovative techniques in skeletal muscle cardiac assistance: first experimental study on minimally invasive aortomyoplasty and cardiomyoplasty.

Skeletal muscle cardiac assistance as a treatment modality for heart failure is considered a high-risk procedure subject to strict patient selection. The aim here is to develop minimally invasive techniques to improve surgical outcomes and increase clinical indications. Ten goats (45-55 kg) were studied. In six, the latissimus dorsi muscle (LDM) was harvested via an open technique on one side vs a minimally invasive technique on the other using video assistance through two 3 cm incisions. Surgical maneuvers and length of procedures were noted. Animals were recovered, observed daily for local complications, and killed after 1 week for comparative anatomic and histopathologic studies. In four other goats, minimally invasive aortomyoplasty or cardiomyoplasty was performed using video assistance (2 aortomyoplasty, 2 cardiomyoplasty). In this experimental series, there were no surgical complications. The minimally invasive LDM harvest required a mean of 81 min (range 55-116 mn) with no gross evidence of muscle damage. The technique of LDM harvesting was standardized and is reproducible. Aortic and cardiac wraping were also achieved through three ports and a left minithoracotomy of 4 cm, using the right or left LDM. A scarf technique for the descending aortomyoplasty using the left LDM, and an anterior wrapping for cardiomyoplasty using the left or right LDM was technically feasible with video assistance. This study suggests future clinical applicability.

Leucovorin and folic acid regimens for selective expansion of murine 5,10-methylenetetrahydrofolate pools.

Mice bearing subcutaneously implanted EMT6 mammary adenocarcinoma were treated with leucovorin or folic acid by continuous subcutaneous infusion or bolus intraperitoneal injection. (6R)-5,10-Methylenetetrahydrofolate pools in cytosolic extracts of the tumor, marrow, and gut were measured by analysis of the ternary complex with thymidylate synthase (5,10-methylenetetrahydrofolate: dUMP C-methyltransferase, EC 2.1.1.45) and 5-fluoro-2'-deoxyuridylate, and the polyglutamate distribution in the (6R)-5,10-methylenetetrahydrofolate pool was analyzed by native gel electrophoresis. Bolus intraperitoneal administration of either leucovorin or folic acid caused dose-dependent expansion of the (6R)-5,10-methylenetetrahydrofolate pool in the tumor, but not in the marrow or gut. For example, the AUC (0-5 hr) in the tumor increased from a baseline value of 8.2 to 20 nmol/mg protein.hr after a bolus dose of 1.5 mmol/kg of leucovorin or folic acid, whereas the increase in marrow and gut was 2- to 4-fold lower. Continuous subcutaneous infusion at the same total dosage over 3 days gave AUC (0-96 hr) values of 134 nmol/mg protein.hr for controls as compared with 347 nmol/mg protein.hr for the leucovorin group and 254 nmol/mg protein.hr for the folic acid group. In contrast to bolus treatment, the increase in (6R)-5,10-methylenetetrahydrofolate in the marrow and small intestine with both leucovorin and folic acid infusion was similar to the increase in the tumor. Thus, intraperitoneal bolus injection was tumor selective, but subcutaneous continuous infusion was not. Longer-chain polyglutamates of (6R)-5,10-methylenetetrahydrofolate in the tumor after bolus treatment with 0.375 and 0.75 mmol/kg of leucovorin or folic acid increased relative to controls. At higher doses of 1.5 and 2.25 mmol/kg, an increase was observed only in the mono/diglutamate fraction. In marrow, on the other hand, the mono/diglutamate fraction, but not the longer-chain polyglutamates, increased at all doses. In the constant infusion regimen, longer-chain polyglutamates increased in all three tissues, though in gut and marrow the mono/diglutamate fraction increased more than in tumor. Leucovorin and folic acid were converted to (6R)-5,10-methylenetetrahydrofolate more efficiently but less selectively during a 3-day subcutaneous infusion than after an intraperitoneal bolus. Longer-chain polyglutamates were selectively increased in tumor by both regimens of leucovorin administration.