Faculty Bibliography

AIMS: The purpose of this study was to determine that the administration of an angiotensin converting enzyme (ACE) inhibitor enalapril would confer protection against doxorubicin-induced experimental heart failure, and attenuate the development of left ventricular dysfunction. METHODS: Seventeen dogs were chronically instrumented with an intracoronary catheter and received doxorubicin weekly for 4 weeks. Animals were assigned to two groups: group 1: untreated heart failure; and group 2: simultaneous enalapril administration (5 mg twice a week). Hemodynamic data were obtained at week 0 and 12. Echocardiography was performed weekly. RESULTS: Survival improved with simultaneous enalapril administration (36% in group 1 vs. 100% in group 2, P=0.04). The increase in the left ventricular end-diastolic pressure was significantly reduced at week 12 (17+/-1 mmHg in group 1 vs. 9+/-1 mmHg in group 2, P=0.0042). The fall in left ventricular stroke work index was significantly prevented (52% in group 1 vs. 21% in group 2, P=0.006). The increase in right ventricular end-diastolic diameter was significantly reduced by enalapril prophylaxis. CONCLUSION: Simultaneous treatment with enalapril was beneficial in the prevention of doxorubicin-induced cardiomyopathy

BACKGROUND: Composite cardiac binding consists of wrapping the heart with a synthetic membrane and a pericardial interposition. The goal of the present study was to apply composite cardiac binding to a canine model of heart failure. METHODS: Twenty dogs were randomized to 2 groups: untreated heart failure (group 1, n = 13) and heart failure pretreated by composite cardiac binding (group 2, n = 7). They received a total dose of 1 mg x kg(-1) of intracoronary doxorubicin over 4 weeks. Hemodynamic data were obtained at weeks 0, 7, and 12. All animals were followed up with weekly echocardiography for 12 weeks. RESULTS: Survival in group 1 was 54% and in group 2 was 100% at week 12 (p = 0.0438). Left ventricular end-diastolic pressure increased by 153% in group 1 and by 59% in group 2 (p = 0.0395) at week 12. Ejection fraction decreased by 27% in group 1 and by 19% in group 2 (p = 0.4401) at week 12. CONCLUSIONS: Composite cardiac binding significantly prolongs survival and attenuates left ventricular dilatation and the increase in left ventricular end-diastolic pressure associated to chronic heart failure. Further evaluation in established heart failure is needed. Composite cardiac binding may be used for the prevention of recurrent dilatation following reduction ventriculoplasty

OBJECTIVE: A porcine model of thoracic aortic graft infection was created, and various anatomic sites and the timing of inoculation of the graft to induce infection were investigated. Ultimately, the ability of cryopreserved allograft to resist infection was compared with that of collagen-impregnated Dacron graft. METHODS: Yorkshire pigs (n = 16) underwent placement of an expanded polytetrafluoroethylene patch graft in the ascending aorta and the left atrial appendage (phase I). Eight animals were immediately given a 50-mL bolus (1 x 10(8) cfu/mL) of Staphylococcus aureus whereas the other 8 received the infusion 24 hours later. Animals were put to death 8 weeks later and the grafts were sterilely explanted and analyzed via microbiologic culture and standard histologic procedures for evidence of infection. The results displayed that the aortic graft and a delay of induced bacteremia of 24 hours were more reliable methods of producing infection. During phase II, 13 pigs were randomized to receive either a collagen-impregnated Dacron graft (n = 6) or a cryopreserved allograft (n = 7) in the ascending aortic position only and infusion of S aureus 24 hours after the operation. The experiment then proceeded to completion. RESULTS: Phase I results displayed that use of an aortic graft and induced bacteremia 24 hours after the operation was a more reliable and reproducible method of producing infection. In phase II, graft infection was present in 38.5% (5/13) of animals, with only 16.7% (1/6) in the collagen-impregnated Dacron graft group and 57.2% (4/7) in the cryopreserved allograft group becoming infected. There was no significant difference between the collagen-impregnated Dacron graft and cryopreserved allograft groups in the incidences of thoracic aortic graft infections (P =.27, Fisher exact test). CONCLUSIONS: This novel porcine model of thoracic aortic graft infection is a reproducible method for the investigation of thoracic aortic graft infections. The phase I study investigated the timing of the induced bacteremia and the most susceptible position of a graft. Phase II demonstrated that collagen-impregnated Dacron grafts are equivalent, if not superior, to cryopreserved allografts in resisting central vascular graft infections in the ascending aorta

The lack of sufficient suitable human donor lungs for the many patients requiring pulmonary transplantation as life-saving therapy for end-stage lung diseases has generated extensive interest in cross-species lung transplantation. Ethical concerns and those of animal rights advocates have prompted studies of nonprimate species as potential solid organ donors for humans. This paper provides an overview of some of the laboratory studies of cross-species pulmonary transplantation performed over the past 20 years and focuses, in particular, on more recent work (from our laboratory and others) in the area of porcine-to-primate pulmonary xenotransplantation

End-stage heart disease is a major health care issue and it represents one of the most costly diseases. Several experimental heart failure models have been developed; however, a single model is not widely accepted as representative of clinical heart failure. The doxorubicin-induced cardiomyopathy model was used in the current study to address two issues: 1) to define a standardized dose regimen of intracoronary doxorubicin infusion; and 2) to establish a method of determining the onset and time course of heart failure. Twenty dogs underwent placement of an intracoronary catheter. A total dose of 1 mg/kg of intracoronary doxorubicin was infused. Hemodynamics were obtained at weeks 0, 7, and 12. Echocardiography was performed weekly. Right and left ventricular biopsy specimens were examined at weeks 0 and 12. Survival after doxorubicin-induced cardiomyopathy was 60% at week 12. The development of heart failure was demonstrated by a significant decrease in left ventricular ejection fraction and cardiac index and a significant increase in left ventricular end-diastolic pressure and volume. The leukocyte count, hemoglobin, and hematocrit decreased significantly. Histologic changes of both the right and left ventricular myocardial biopsy specimens included myocellular hypertrophy, loss of myofibrillar material, and vacuolization. Intracoronary doxorubicin reliably produced an experimental model of accelerated heart failure that developed over the course of 12 weeks. Echocardiographic monitoring allowed a close surveillance of heart failure development. This model may be useful to evaluate the efficacy of cardiomyoplasty, mechanical assist devices, transplantation, and reduction ventriculoplasty

BACKGROUND: Cardiomyoplasty is a potential therapy for heart failure. Its benefits are attributed to systolic augmentation (dynamic cardiomyoplasty) and prevention of cardiac dilatation (static cardiomyoplasty). To evaluate the static component, we used an artificial membrane for cardiac binding in a canine model of heart failure. METHODS: Intracoronary doxorubicin was administered weekly for 4 weeks to induce heart failure in 10 dogs, each of which was assigned to one of two treatment groups: (1) no treatment, or (2) cardiac binding. Hemodynamic data were obtained at operation and at 7 weeks after operation. Echocardiography was performed weekly. RESULTS: Left ventricular end-diastolic pressure and diameter, and right ventricular end-diastolic diameter increased in group 1 (from 9.6 +/- 6.1 to 19.6 +/- 2.3 mm Hg, p = 0.009; from 3.9 +/- 0.4 to 5 +/- 0.3 cm, p = 0.0013; and from 1.6 +/- 0.2 to 1.9 +/- 0.3 cm, p = 0.0036, respectively). Ejection fraction fell in group 1 from 0.60 +/- 0.10 to 0.40 +/- 0.04 (p = 0.0009) and in group 2 from 0.56 +/- 0.02 to 0.40 +/- 0.04 (p = 0.0001), but the difference between groups was not significant. CONCLUSION: Cardiac binding reduces the ventricular dilatation associated with heart failure without exacerbating left ventricular dysfunction

Prolonged pleural effusion after congenital heart surgery results in extended hospitalization. Pleural drainage was evaluated in 39 consecutive patients undergoing repair of tetralogy of Fallot, to identify risk factors for persistent pleural effusion. Duration and amount of drainage was examined by the Kaplan-Meier method and risk factors were evaluated by univariable and multivariable analyses. Median time of pleural drainage was 6.1 days, range 3 to 42 days. Duration of pleural drainage correlated with length of hospital stay (p < 0.0001). Postrepair right atrial pressure (p = 0.018) and preoperative hemoglobin (p = 0.035) were risk factors for persistent drainage. The presence of a previous right thoracotomy reduced drainage duration (p = 0.034). Prolonged mechanical ventilation increased the average daily volume of effusion (p < 0.0001). In conclusion, prolonged pleural effusion is an important morbidity factor after repair of tetralogy of Fallot. Bilateral chest tube insertion is indicated in patients with high preoperative hemoglobin and elevated postrepair right atrial pressure. Right thoracotomy is the preferred surgical approach when a preliminary palliative shunt is required

Latissimus dorsi muscle (LDM) transformation following chronic stimulation is the critical requirement for its use in cardiac assist procedures. In order to identify one or two molecular markers that can be used to effectively monitor the LDM transformation, the modulation in the expression of creatine kinase (CK) and phospholamban (PLB) genes by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was examined. Continuous in situ stimulation of left LDM was performed in four dogs for a period of 10 weeks after a vascular delay period of 2 weeks following surgery. For RT-PCR, gene-specific radiolabeled primers and equal amounts of cDNA synthesized from total RNA extracted from the LDM biopsies obtained at 4, 7, and 10 weeks of stimulation were used. A 2.6-fold increase in creatine kinase (brain type) (CK-B) mRNA was observed at transformed LDM compared to the control (P = 0.004) following 10 weeks of stimulation. On the contrary, a 30% decline was observed in creatine kinase (muscle type) (CK-M) mRNA level. An increase up to eight-fold was also observed in PLB mRNA in stimulated LDM compared to the contralateral muscle (P = 0.002). The PLB mRNA level in transformed LDM reached plateau and became comparable to that of normal heart after 7 weeks of stimulation. However, a sustained increase in CK-B mRNA level was observed until 10 weeks of stimulation. The level of beta-actin mRNA used as control remained the same in both stimulated and control samples. Thus the increase in CK-B and PLB mRNA and downregulation of CK-M mRNA in transformed LDM, demonstrated here by RT-PCR, indicate a switch from anaerobic to aerobic potential of transformed LDM along with a change towards slow-twitch phenotype and provide valuable markers to monitor the effectiveness of muscle transformation in cardiomyoplasty