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Biomedical subjects

Franklin L Rosenfeldt

Publications and source records attributed to Franklin L Rosenfeldt.

17 recordsLinked to original sources

Polyethyleneterephthalate provides superior retention of endothelial cells during shear stress compared to polytetrafluoroethylene and pericardium.

BACKGROUND: Polyethyleneterephthalate (PET) and polytetrafluoroethylene (PTFE) are polymers successfully used as large diameter arterial grafts for peripheral vascular surgery. However, these prosthetic grafts are rarely used for coronary bypass surgery because of their low patency rates. Endothelialisation of the lumenal surface of these materials may improve their patency. This study aimed to compare the endothelialisation of PET, PTFE and pericardium by examining their seeding efficiency over time and the effect of various shear stresses on retention of endothelial cells. METHODS: Ovine endothelial cells at 4x10(5)cells/cm(2) were seeded onto PET, PTFE and pericardium, and cultured for 1-168 hours. Cell coverage was determined via en face immunocytochemistry and cell retention was quantified after being subjected to shear stresses ranging from 0.018 to 0.037N/m(2) for 15, 30 and 60 minutes. RESULTS: Endothelial cells adhered to all of the materials one hour post-seeding. PET exhibited better cell retention rate, ranging from 66.9+/-5.6% at 0.018N/m(2) for 15min to 44.7+/-1.9% at 0.037N/m(2) for 60 minutes, when compared to PTFE and pericardium (p<0.0001, three-way ANOVA). CONCLUSION: PET shows superior retention of endothelial cells during shear stress compare to PTFE and pericardium.

Animals↗

Early institution of mechanical support improves outcomes in primary cardiac allograft failure.

BACKGROUND: Primary graft failure (PGF) is the leading cause of early mortality after cardiac transplantation, accounting for 27.1% of deaths within 30 days. PGF is defined as severe dysfunction of the cardiac allograft without any obvious anatomic or immunological cause. The purpose of this study was to analyze our last 9 years of experience with cardiac transplantation to determine predictors of PGF and the influence on survival of our policy of early institution of mechanical circulatory support (MCS) in these patients. METHODS: Data on 214 consecutive cardiac transplants performed at The Alfred Hospital between January 1996 and August 2004 were reviewed. PGF was defined as right or left or biventricular failure manifesting as hypotension (systolic blood pressure <90 mm Hg), low cardiac output (cardiac index <2.0 liter/min/m2 and pulmonary capillary wedge pressure >20 mm Hg after coming off cardiopulmonary bypass despite inotropic support of up to 5 mug/min adrenaline and without any other obvious cause for the graft dysfunction. RESULTS: PGF developed in 51 patients (24%). Significant factors in the development of PGF were long ischemic time, which became significant over 4 hours (odds ratio, 1.43; p = 0.01) and increased donor age (odds ratio, 1.027; p = 0.045). Fifteen patients required mechanical support, and of these, 10 survived to leave hospital. CONCLUSIONS: PGF is the major cause of early mortality after cardiac transplantation. Significant risks for PGF are long allograft ischemic time and increased donor age. Once the patient has survived 30 days, however, the longer-term survival is not influenced by PGF. Our management strategy of early mechanical support has yielded good outcomes in this population with a high risk of early death.

Age Factors↗

First clinical implant of the VentrAssist left ventricular assist system as destination therapy for end-stage heart failure.

The VentrAssist device left ventricular assist system, designed for permanent implantation, is a novel centrifugal pump with a hydrodynamically suspended rotor. The first human implant was into a 72-year-old man with New York Heart Association (NYHA) class IV heart failure due to idiopathic dilated cardiomyopathy. The implant and recovery were uneventful, and the patient survives at 17 months, is NYHA class II, and lives at home. This device shows promise in end-stage heart failure for permanent implantation and bridge to transplantation.

Aged↗

The split radial technique: an alternative to the Y-graft for total arterial myocardial revascularisation.

There is evidence that the use of Y-grafts attached to the left internal mammary artery - to - left anterior descending artery graft may compromise the patency of the distal limb of the left internal mammary artery. We describe a technique (split radial technique) that avoids the use of Y-grafts by constructing two aorto-coronary grafts from a single radial artery. The split radial technique requires the harvesting of the radial artery in its entirety from the brachial bifurcation to the radial styloid. The first radial artery distal anastomosis is performed and the required length of conduit is determined. The conduit is transected, leaving a sufficiently long radial segment for a second aorto-coronary graft. A clinical follow-up 41 weeks after surgery of the first 37 patients in whom the split radial technique was used showed no deaths or major complications. This suggests that the split radial technique is a useful and safe way to maximise the use of radial artery conduit and to avoid the potential risk of compromising internal mammary artery patency with Y-grafts. There is evidence that the use of Y-grafts attached to the left internal mammary artery may compromise the patency of the distal limb of the left internal mammary artery. We describe the split radial technique of constructing two aorto-coronary graft segments from a single radial artery that can be used to avoid the use of Y-grafts.

Aged↗

Skeletal myopathy associated with nucleoside reverse transcriptase inhibitor therapy: potential benefit of coenzyme Q10 therapy.

Zidovudine (ZDV) has been associated with 'ragged-red' fibre myopathy, due to its effects on myocyte mitochondria. Usually this is reversible with cessation of ZDV. We report a 52-year-old man, who in 1985 developed ragged-red fibre myopathy 14 years after diagnosis of HIV infection while on effective ZDV-based combination antiretroviral therapy (ART). He was treated with the mitochondrial anti-oxidant coenzyme Q10 and made an excellent recovery, without change of ARTs. This suggests a novel therapy for further investigation targeted at ZDV induced myopathy, potentially allowing continuation of antiviral treatments including ZDV.

Acquired Immunodeficiency Syndrome↗

Heterotopic heart transplantation: an expanding role in the twenty-first century?

BACKGROUND: Heterotopic heart transplantation was first performed in humans in 1974, the main advantage being the continuing function of the patient's native heart, in the event of life-threatening acute rejection. The effect of cyclosporine on acute rejection saw the heterotopic transplantation technique wane. Our unit revisited heterotopic transplantation in response to a growing number of waiting list patients with high pulmonary artery pressures. We also anticipated an increased cardiac allograft utilization, and improvement of our waiting list times. METHODS: We retrospectively analyzed 151 patients undergoing heart transplantation by our unit between August 1997 and September 2003. Twenty received allografts in the heterotopic position. This cohort was compared with the 131 contemporary orthotopic heart transplant recipients with respect to their outcomes. RESULTS: The indication for transplantation was ischemic cardiomyopathy in 14 (70%) of the heterotopic cohort and 47 (36%) of the orthotopic cohort (p = 0.004), and dilated cardiomyopathy in 3 (15%) and 48 (37%) in the heterotopic and orthotopic groups, respectively (p = 0.06). Heterotopic recipients were significantly older than orthotopic recipients, and they had higher pulmonary artery pressures. The heterotopic donors were also older and the ischemic times were longer. A subgroup analysis was made among those patients who had high pulmonary artery pressures as these groups were better matched. Major morbidity in the heterotopic heart transplantation group consisted of reversible allograft dysfunction in 4 patients, renal dysfunction requiring hemofiltration in 3 patients, profound myopathy in 4 patients, and cerebrovascular events in 2 patients. There were two early deaths in the heterotopic transplant group and eight in the orthotopic group (p = 0.87). Kaplan-Meier survival analysis of survival was performed. CONCLUSIONS: Heterotopic heart transplantation is a viable transplant option for selected high-risk heart transplant recipients in spite of somewhat poorer outcomes.

Acute Kidney Injury↗

The challenge of improving donor heart preservation.

Heart transplantation has in recent years become the treatment of choice for end stage heart failure. However while the waiting list for transplantation is growing steadily, the donor pool is not increasing. Therefore, in order to meet demand, transplant programs are using older, "marginal donors" and accepting longer ischaemic times for their donor hearts. As donor organs are injured as a consequence of brain death, during the period of donor management, at organ harvest, preservation, implantation and reperfusion, expansion of acceptance criteria places a great burden on achieving optimal long-term outcomes. However, at each step in the process of transplantation strategies can be employed to reduce the injury suffered by the donor organs. In this review, we set out what steps can be taken to improve the quality of donor organs.

Journal Article↗

Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age.

Deletions in mitochondrial DNA (mtDNA) accumulate with age in humans without overt mitochondriopathies, but relatively limited attention has been devoted to the measurement of the total number of mtDNA molecules per cell during ageing. We have developed a precise assay that determines mtDNA levels relative to nuclear DNA using a PCR-based procedure. Quantification was performed by reference to a single recombinant plasmid standard containing a copy of each target DNA sequence (mitochondrial and nuclear). Copy number of mtDNA was determined by amplifying a short region of the cytochrome b gene (although other regions of mtDNA were demonstrably useful). Nuclear DNA content was determined by amplification of a segment of the single copy beta-globin gene. The copy number of mtDNA per diploid nuclear genome in myocardium was 6970 +/- 920, significantly higher than that in skeletal muscle, 3650 +/- 620 (P = 0.006). In both human skeletal muscle and myocardium, there was no significant change in mtDNA copy number with age (from neonates to subjects older than 80 years). This PCR-based assay not only enables accurate determination of mtDNA relative to nuclear DNA but also has the potential to quantify accurately any DNA sequence in relation to any other.

Adolescent↗

Occlusive wrap dressing reduces infection rate in saphenous vein harvest site.

BACKGROUND: Infection in the saphenous vein harvest site is a common problem. We developed an occlusive circumferential wrap dressing technique that reduces skin edge tension, eliminates dead space, and prevents external contamination. We compared the surgical site infection rate using the wrap dressing technique with that of standard longitudinal dressings. METHODS. One hundred fifty-two consecutive patients were randomly assigned to receive either standard dressings or the wrap dressing. Data were collected in the hospital and then 4 to 6 weeks postoperatively. Superficial and deep wound infections were defined by the standard criteria from the Centers for Disease Control and Prevention. RESULTS: The infection rate in the wrap group was 14% compared with 35%, for the standard group (p = 0.006). Multivariate analysis showed that wrap technique was the only significant predictor (negative) of infection (odds ratio, 0.19; p = 0.001). CONCLUSIONS: In saphenous vein harvest wounds, the occlusive wrap dressing technique has the potential to reduce the rate of infection by 50%. This simple and inexpensive technique is also readily applicable to the radial artery harvest site in the arm and may provide similar benefit.

Aged↗

Endogenous cardiac opioids: enkephalins in adaptation and protection of the heart.

Opiates have been used for thousands of years in the form of opium for relief of pain or fever and to induce sleep. However, it was only in the 1970s that the endogenous ligands for the opiate receptors were identified and termed opioid peptides. Opioid peptides activate G protein-coupled receptors in the central and autonomic nervous system, with marked effects on the regulation of pain perception, body temperature, respiration, heart rate and blood pressure. Cardiovascular regulatory effects of endogenous opioids were initially considered to originate from neural centres in the central nervous system, facilitating a regulatory role in neuro-transmission, as demonstrated by the presynaptic co-release from sympathetic neurones of norepinephrine with enkephalin or acetylcholine with enkephalin. However, opioid peptides of myocardial origin have also recently been shown to play a key role in local regulation of the heart. This brief review highlights the key features of the enkephalin opioids in the heart and the current understanding of their role in development, ageing, cardioprotection, hypertension, hypertrophy, and heart failure.

Journal Article↗

In vitro comparison of glyceryl trinitrate-verapamil with other dilators of human saphenous vein.

BACKGROUND: A common problem encountered during harvesting of the saphenous vein for coronary artery bypass grafting (CABG) is spasm of the vein. The previous work of the present authors has led to the development of a dilator solution containing glyceryl trinitrate (GTN) and verapamil for use during harvesting of the saphenous vein (SV) and the internal mammary artery. The present organ bath study was designed (i) to determine the best vasodilator agents for the saphenous vein during harvesting and (ii) to investigate the presence of any synergistic effect when vasodilator agents are combined. METHODS: Discarded segments of saphenous vein were collected from 46 patients undergoing CABG and studied in organ baths. Initially veins were contracted with potassium or thromboxane A2 mimetic (U46619). Dilators were added individually or in combination in clinically relevant concentrations to study time of onset and maximum effect. The vasodilator agents tested included GTN, verapamil (V), sodium nitroprusside (SNP) and nicorandil (N). RESULTS: When rapidity of onset (i.e. relaxation caused in the first minute) was considered, GTN or combinations containing GTN, caused a response that was significantly faster than the other vasodilators (P < 0.05). The maximum response caused by the GTN-V combination (61.4 +/- 9.6%) was significantly greater than all the other single dilators, SNP (35 +/- 4%) and N (10 +/- 3%) (P < 0.05). However, no synergistic effects were demonstrated. CONCLUSIONS: The present paper demonstrates the following conclusions: (i) glyceryl trinitrate is a rapidly acting dilator of the human isolated SV. (ii) GTN-V combination is a potent combination causing a maximum dilator effect that is significantly greater than single agents including SNP and N.

Aged↗

Initial in vivo experience of the VentrAssist implantable rotary blood pump in sheep.

VentrAssist (VentrAssist Division, Ventracor Ltd., Chatswood, NSW, Australia) has developed an implantable centrifugal blood pump with an integrated rotor and impeller that is hydrodynamically suspended. Bench testing has been used to assess the performance of the pump under a broad range of operating conditions. This study examined the performance of the pump in vivo up to 90 days implantation. Pumps were implanted via a left lateral thoracotomy. The inflow cannula was inserted at the apex of the left ventricle. The outflow cannula was anastomosed to the descending thoracic aorta. Eighteen implants were performed. Poor recovery from surgery was the main cause of early study termination. These studies demonstrate the suitability of the animal model for evaluation of the VentrAssist rotary blood pump. Further in vivo studies prior to preclinical trials are in progress.

Animals↗

The effects of ageing on the response to cardiac surgery: protective strategies for the ageing myocardium.

UNLABELLED: With ageing of the general population, increasing numbers of elderly patients are presenting for interventional cardiac treatment such as cardiac surgery, angioplasty and thrombolysis. However, the results of these interventions in the elderly are inferior to those in the young. A likely contributing factor is an age-related reduction in cellular energy production in the myocardium during interventions that induce aerobic or ischaemic stress. Coenzyme Q10 (CoQ10) has the potential to improve the efficiency of energy production in mitochondria by bypassing defective components in the respiratory chain as well as reducing the effects of oxidative stress. We hypothesised that CoQ10 pretreatment prior to stress could improve the post-stress recovery of the myocardium. We investigated this hypothesis in three studies. In Study 1, isolated hearts taken from senescent or mature rats, pre-treated with CoQ10 were subjected to rapid electrical pacing and the recovery of work after pacing as a percentage of pre-pacing level was measured. In Study 2, human atrial tissue obtained at the time of open heart surgery was subjected to simulated ischaemia in the organ bath after incubation with CoQ10 or vehicle and recovery measured. Study 3 was a clinical trial of oral CoQ10 therapy for 2 weeks pre-operatively in patients undergoing elective cardiac surgery. Study 1. CoQ10 treatment in senescent rat hearts improved recovery of work after rapid pacing (48.1+/-4.1 vs 16.8+/-4.3%; P < 0.0001) and MVO2 (82.1+/-2.8 vs 61.3+/-4.0%; P < 0.01) in treated versus untreated hearts respectively. Study 2. Post-ischaemic human trabeculae from the > or =70 years old group displayed less contractile recovery compared to the <70 years old group, but this difference was abolished by CoQ10 pre-incubation. Study 3: respiration by mitochondria isolated from trabeculae was more efficient after CoQ10 pretreatment than placebo. Compared to placebo, CoQ10 patients had a lower release of Troponin I, improved cardiac pump function and a shorter length of stay in hospital. IN CONCLUSION: 1) Senescent hearts have reduced baseline function and reduced tolerance to aerobic stress compared to young hearts. 2) Pre-treatment with oral CoQ10 improves baseline function of the senescent myocardium and its tolerance to aerobic stress. 3) CoQ10 pre-treatment in vitro overcomes the reduced capacity of aged human heart muscle to recover contractile function after ischaemia compared to younger muscle. 4) Oral CoQ10 therapy before cardiac surgery improves efficiency of mitochondrial energy production, improves post-operative heart function, reduces intra-operative myocardial damage and shortens hospital stay.

Aged↗

Coenzyme Q10 protects the aging heart against stress: studies in rats, human tissues, and patients.

With aging of the population, increasing numbers of elderly patients are presenting for cardiac surgery. However, the results in the elderly are inferior to those in the young. A likely contributing factor is an age-related reduction in cellular energy production in the myocardium during surgery, which is known to induce aerobic and ischemic stress. The lipophilic antioxidant and mitochondrial respiratory chain redox coupler, coenzyme Q10 (CoQ10), has the potential to improve energy production in mitochondria by bypassing defective components in the respiratory chain as well as by reducing the effects of oxidative stress. We hypothesized that CoQ10 pretreatment prior to stress could improve the recovery of the myocardium after stress.

Aged↗