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Franklin Rosenfeldt

Publications and source records attributed to Franklin Rosenfeldt.

17 recordsLinked to original sources

Pre-operative preparation for cardiac surgery utilising a combination of metabolic, physical and mental therapy.

UNLABELLED: Cardiac surgery represents major metabolic, physical and mental stresses associated with an increased production of reactive oxygen species. These stresses may hamper post-operative recovery, increasing hospitalisation times and operative mortality. We conducted a quality assurance and feasibility study to evaluate and monitor the safety and efficacy of a new program of combined pre-operative metabolic (enhanced antioxidant), physical and mental therapy to counter these stresses prior to cardiac surgery. METHODS: Sixteen cardiac surgery patients received metabolic therapy consisting of the antioxidants coenzyme Q(10) (CoQ(10)) (300 mg) and alpha-lipoic acid (300 mg), combined with magnesium orotate (1200 mg), and omega-3 fatty acids (3g) given daily for a mean 36+/-7 days up until the day of operation. Patients also received a regimen of physical therapy incorporating non-exhaustive, light exercise and stretching techniques. Mental therapy in the form of stress reduction, relaxation and music was also provided. Blood levels of CoQ(10) and malondialdehyde (MDA) were measured and a quality of life (QoL) questionnaire (SF-36) was administered before, after the program and 1 month after surgery. A patient satisfaction survey was conducted at six weeks post-operatively. RESULTS: During the pre-operative period, treated patients (n=16) showed significant improvements in QoL composite scores, physical (33.5+/-4.1 to 41.0+/-4.5, p=0.005) and mental (44.3+/-4.5 to 54.1+/-5.3, p=0.006). CoQ(10) levels increased from 725.6+/-96.1 nmol/l to 3019.9+/-546.4 nmol/l (p=0.006), MDA levels decreased from 2.2+/-0.9 microM to 1.4+/-0.7 microM (p=0.013) and systolic blood pressure decreased from 140+/-4.0 mmHg to 132+/-3.0 mmHg (p=0.002). One month after surgery the treated group (n=14) demonstrated significant improvements from pre-operative baseline in QoL composite scores, physical (38.9+/-4.0 to 57.9+/-5.4, p=0.01) and mental (50.3+/-5.6 to 69.3+/-4.8, p=0.03) compared to a previously reported similar group of cardiac surgery patients (n=74) whose physical and mental scores decreased from 43.0 to 42.8 (p=0.05) and 53.8 to 49.8, respectively (p=0.05). CONCLUSION: These preliminary results suggest that a program of combined metabolic, physical and mental preparation before cardiac surgery is safe, feasible and may improve quality of life, lower systolic blood pressure, reduce levels of oxidative stress and thus has the potential to enhance post-operative recovery.

Aged↗

Techniques of reconstruction for inadequate donor left atrial cuff in lung transplantation.

BACKGROUND: An inadequate donor left atrial (LA) cuff due to an anatomical abnormality of the pulmonary vasculature or technical errors at the time of procurement can exclude the lungs from transplant. This study aims to describe the incidence, efficacy, and various techniques of LA cuff reconstruction in lung transplantation. METHODS: A total of 637 pulmonary venous anastomosis in 405 consecutive lung transplants from January 1995 to July 2005 were reviewed. Comparison between the patients who required LA cuff reconstruction (reconstruction group) or who did not (no-reconstruction group) was made in posttransplant outcomes. RESULTS: An overall incidence of requirement of LA cuff reconstruction was 2.7% (4% on the right, 1% on the left, p = 0.03). Seventy-one percent of LA inadequacy was corrected using a pericardial patch on the anterior LA cuff wall; the remainder required complicated reconstruction for separated/short pulmonary veins to create a new LA cuff. There was no significant difference between the reconstruction and no-reconstruction groups, respectively, in oxygenation (329 +/- 28, 337 +/- 10, p = 0.81), duration of intubation and intensive care unit stay (p = 0.54, p = 0.89, respectively), 30-day mortality (12%, 6%, p = 0.30), and 5-year survival (57%, 52%, p = 0.80). CONCLUSIONS: Inadequate donor LA cuff is an infrequent but potentially serious complication in lung transplantation. Donor LA cuff reconstruction using donor pericardium or pulmonary artery remnant is a useful technique to salvage surgically marginal lungs without affecting early and late posttransplant outcomes. These lungs should not be excluded from transplantation.

Adult↗

Evaluation of techniques for lung transplantation following donation after cardiac death.

BACKGROUND: Lung transplantation using "donation after cardiac death" donors is a potential means to alleviate the shortage of suitable donor lungs for transplantation, but the practicality and utility of the various possible techniques need to be clarified. METHODS: Using a dog model, we explored seven variations of standoff (ischemic) time (50 to 240 minutes), topical cooling (60 to 120 minutes), and flush cooling and cold storage (30 to 140 minutes) to mimic different human donor lung retrieval scenarios that can follow donation after cardiac death. The functional status of donation after cardiac death donor lungs was assessed initially with a 250 mL pulmonary arterial blood flush while ventilating with 100% oxygen and then on an ex-vivo perfusion rig for 120 minutes after retrieval. RESULTS: All lungs achieved an excellent pO2/FiO2 ratio ranging from 472 to 586 with stable pulmonary artery pressures and pulmonary vascular resistance and no net weight gain (952 +/- 221 g versus 1,006 +/- 235 g) during the 120-minute evaluation period. Initial blood flush correlated well with measured perfusion rig pO2 at 30 minutes (R2 = 0.63). CONCLUSIONS: This canine study suggests that lungs donated after cardiac death are reproducibly useable for transplantation with ischemic times of as long as 60 minutes. Although more study is needed, a blood flush evaluation is simple and may have a role as a secondary allograft assessment tool. The existing techniques of donor lung evaluation and preservation after donation following cardiac death thus appear both feasible and practical.

Animals↗

Early outcomes comparing Perfadex, Euro-Collins, and Papworth solutions in lung transplantation.

BACKGROUND: Despite improved surgical techniques and medical management, primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after lung transplantation. Different types of lung preservation solutions have been developed and applied to clinical use; however, the relative clinical efficacy of these solutions to prevent PGD remains controversial. This study aimed to investigate the effect of the three solutions most commonly used (Perfadex [Vitrolife, Göteborg, Sweden], Papworth, and Euro-Collins [Baxter Healthcare, Old Toongabbie NSW, Australia]) on posttransplant outcomes. METHODS: Early outcomes from 157 consecutive lung transplants (113 bilateral and 44 single) performed at The Alfred Hospital were compared across three preservation solutions. RESULTS: Posttransplant oxygenation (p = 0.57), pulmonary vascular resistance (p = 0.34), intubation hours (p = 0.66), intensive care unit days (p = 0.34), severe PGD (grade 3) (p = 0.70), 30-day mortality (p = 0.87), and 3-month % predicted forced expiratory volume in 1 second (p = 0.58) were not statistically different; however, Perfadex trended toward superiority among the three solutions. After adjustment of donor, recipient, and operative factors in multivariate analysis, Perfadex was significantly associated with the prevention of moderate to severe PGD (grade 2 to 3) at 48 hours posttransplant (odds ratio = 0.26 [0.10 to 0.72], p < 0.01) compared with Papworth (odds ratio = 0.75 [0.32 to 1.75], p = 0.51) and Euro-Collins (reference) solutions. CONCLUSIONS: Although any advantageous effects of Perfadex on early posttransplant outcomes were generally subtle and statistically nonsignificant, Perfadex prevented moderate to severe PGD. Switching preservation solution from Euro-Collins (or Papworth) to Perfadex would appear to usefully contribute to a strategy to reduce PGD in lung transplantation.

Adult↗

High-flow endobronchial cooled humidified air protects non-heart-beating donor rat lungs against warm ischemia.

OBJECTIVE: Lungs from non-heart-beating donors for transplantation require protection against warm ischemic damage. Minimally invasive techniques are required to reduce organ damage during the warm ischemic period because invasive surgical procedures are often not feasible at this time. This study investigated the preservative effect of high-flow endobronchial cooled humidified air during warm ischemia in non-heart-beating donor rat lungs. METHODS: Fourteen animals were divided into a Cooling group (n = 7), which received cooled air/saline spray during a 2-hour warm ischemic period, and a Control group (n = 7), which received no cooling. After ischemia the lungs were reperfused on an isolated lung perfusion apparatus. RESULTS: Endobronchial temperatures in the Cooling and Control groups were 8 degrees C and 36 degrees C at 10 minutes, and 5 degrees C and 35 degrees C at 20 minutes, respectively (P < .0001). Lung core and surface temperatures in the Cooling group were also lower than those in the corresponding Control group (P < .0001). After reperfusion, pulmonary arterial pressure (P = .003) and peak airway pressure (P = .002) were lower in the Cooling group than in the Control group. Higher pulmonary venous PO2 (P = .02), higher adenosine triphosphate levels (P = .01), and lower wet/dry lung weight ratio (P = .003) were seen in the Cooling group compared with the Control group. CONCLUSIONS: High-flow endobronchial cooled humidified air can decrease lung temperature and improve post-ischemic pulmonary function and adenosine triphosphate levels in non-heart-beating donor lungs.

Adenosine Triphosphatases↗

Total leukocyte control for elective coronary bypass surgery does not improve short-term outcome.

BACKGROUND: Despite early promise as a means of reducing the inflammatory response to surgery and subsequent organ damage, the evidence of the clinical value of leukocyte filtration remains equivocal. METHODS: Three hundred patients presenting for routine coronary artery bypass surgery were randomized to a total leukocyte filtration group (filters in five different locations) and a control group with a standard 40-mum filter in the bypass return line only. Data on efficacy and safety of leukocyte filtration were collected by research and postoperative care staff who were blinded to the mode of filtration. RESULTS: Leukofiltration achieved a transient fall in white cells immediately after surgery (p = 0.07) and a sustained fall in platelets, which was still significant on the second postoperative day (p = 0.0001). However, there were no significant differences in postoperative hospital stay, the primary outcome variable (p = 0.35), in ICU stay (p = 0.92), or mortality (p = 1.0). There were no differences in postoperative cardiac status including cardiac output (p = 0.16), inotrope (p = 0.93) or balloon pump (p = 0.48) requirement, or 24-hour troponin (p = 0.60). Similarly there were no differences in pulmonary or renal function (intubation time (p = 0.83), respiratory index (p = 0.19) rise in creatinine (p = 0.13) or hemofiltration (1.0)). Leukofitration was not associated with a statistically significant increase in bleeding or requirement for blood or blood products. It was associated with a decrease approaching significance (p = 0.1) in number and severity of postoperative wound infections. Three filters were blocked during use but were changed without incident or compromise to patient safety. CONCLUSIONS: Leukocyte filtration is safe but not efficacious in improving short-term outcome.

Aged↗

Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue.

OBJECTIVES: Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery. METHODS: Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed. RESULTS: Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I. CONCLUSIONS: Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.

Administration, Oral↗

Extracorporeal membrane oxygenation after lung transplantation: evolving technique improves outcomes.

BACKGROUND: Severe pulmonary graft failure (PGF) is the most common cause of death within the first 30 days after lung transplantation. Extracorporeal membrane oxygenation (ECMO) may provide lifesaving temporary support; however, its longer-term efficacy is controversial. METHODS: We reviewed the use of ECMO for severe PGF after lung transplantation, and compared the outcomes between our early (1990 to 1999) and recent (2000 to 2003) experience utilizing improved initiation timing, oxygenator technology, and surgical technique. RESULTS: Ten transplant recipients from a total of 481 (2.1%) were managed for PGF on ECMO by a multidisciplinary team at The Alfred Hospital. Four single-lung, 3 bilateral single-lung, and 3 heart-lung recipients were supported for a mean of 96 hours (range 14 to 212 hours). In the early group (operation from 1990 to 1999, n = 4) ECMO was initiated 21 days (range 7 to 40 days) after lung transplantation and in the recent group (operation from 2000 to 2003, n = 6) after 0 to 2 days (p = 0.01). Radial-arterial blood gas analysis 12 hours after initiation of ECMO showed significantly better oxygenation in the recent group (341 +/- 90 mm Hg) than in the early group (90 +/- 23 mm Hg, p = 0.03). Four deaths occurred as a result of bleeding (two in each group). In the early group only 1 patient was weaned from ECMO but died. In the recent group 3 were successfully weaned and were discharged from the intensive care unit; of these patients, 2 were discharged from hospital. CONCLUSIONS: Extracorporeal membrane oxygenation results have improved with advances in oxygenator technology and surgical techniques. The procedure can allow resolution of early PGF after lung transplantation.

Adolescent↗

Response of the senescent heart to stress: clinical therapeutic strategies and quest for mitochondrial predictors of biological age.

The aging heart has an impaired response to many kinds of stress. In clinical practice, there is a need for senescence-specific therapies to protect against stress and for biochemical markers of senescence to identify those patients most in need of therapy. In isolated rat hearts, in human tissues, and in a clinical trial, we have shown previously that coenzyme Q(10) has the ability to protect the heart against stress especially in senescence. We recently have devised a regimen of therapy to protect the senescent heart against stress, combining metabolic therapy (coenzyme Q(10), alpha lipoic acid, magnesium orotate, and omega 3 polyunsaturated fatty acids) with physical exercise and mental stress reduction. The preliminary results of this program are promising. In an endeavor to predict the likely response of individual senescent hearts to stress, we correlated the tissue load of mitochondrial DNA deletions and total cellular mitochondrial DNA copy number in human cardiac tissue with recovery of the same tissue from ischemia/reperfusion stress. We found that these mitochondrial markers actually were less predictive of impaired response to stress than age alone. We conclude that the aging heart has a diminished capacity to recover from stress that is not readily predictable by cardiac content of intact mitochondrial DNA and that this recovery can be improved by metabolic therapy combined with physical exercise and mental stress reduction.

Aging↗

Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure.

COENZYME Q10 IN PHYSICAL EXERCISE. We identified eleven studies in which CoQ10 was tested for an effect on exercise capacity, six showed a modest improvement in exercise capacity with CoQ10 supplementation but five showed no effect. CoQ10 IN HYPERTENSION. We identified eight published trials of CoQ10 in hypertension. Altogether in the eight studies the mean decrease in systolic blood pressure was 16 mm Hg and in diastolic blood pressure, 10 mm Hg. Being devoid of significant side effects CoQ10 may have a role as an adjunct or alternative to conventional agents in the treatment of hypertension. CoQ10 IN HEART FAILURE. We performed a randomised double blind placebo-controlled pilot trial of CoQ10 therapy in 35 patients with heart failure. Over 3 months, in the CoQ10 patients but not in the placebo patients there were significant improvements in symptom class and a trend towards improvements in exercise time. META-ANALYSIS OF RANDOMISED TRIALS OF COENZYME Q10 IN HEART FAILURE. In nine randomised trials of CoQ10 in heart failure published up to 2003 there were non-significant trends towards increased ejection fraction and reduced mortality. There were insufficient numbers of patients for meaningful results. To make more definitive conclusions regarding the effect of CoQ10 in cardiac failure we recommend a prospective, randomised trial with 200-300 patients per study group. Further trials of CoQ10 in physical exercise and in hypertension are recommended.

Cardiac Output, Low↗

The principles of metabolic therapy for heart disease.

Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. First, for some systems, a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Second, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapy such as the use of ACE Inhibitors b-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes. In this review we highlight some metabolic substances that have potential benefit in treating heart disease or improving outcomes after cardiovascular interventions. Glucose-insulin-potassium therapy is protective against myocardial ischaemia by elevating myocardial glycogen levels. Coenzyme Q(10) is a lipid-soluble antioxidant that plays a crucial role in cellular ATP production. Magnesium orotate, a key intermediate in the biosynthetic pathway of glycogen, has been shown to improve the energy status of the cell and improve recovery from cardioplegic arrest. The amino acid aspartate plays an important role in providing energy substrates for oxidative phosphorylation in the myocyte. By improving cellular energy production, metabolic therapy has the potential to benefit cardiac function during the stress of cardiac surgery, myocardial infarction and cardiac failure.

Journal Article↗