Low-flow hypothermic crystalloid perfusion is superior to cold storage during prolonged heart preservation.

BACKGROUND: Preservation of donor hearts for transplantation has traditionally been performed with the use of static cold storage. We have developed and tested a novel gravity-powered system of cold crystalloid perfusion for prolonged donor heart preservation. METHODS: Greyhounds were anesthetized; their hearts were arrested with cold cardioplegic solution and excised. Hearts were allocated to 12 hours of perfusion preservation (n = 6) or cold storage in ice (n = 5). Non-preserved hearts (n = 5) served as a normal reference group. Perfusion hearts were perfused (20 mL/min, 8-12°C) with a novel oxygenated nutrient-containing preservation solution. After preservation, the recovery of the hearts was assessed in a blood-perfused working heart rig over 2 hours in terms of function, blood lactate level, myocardial adenosine triphosphate, and histology. RESULTS: After 2 hours of reperfusion, in comparison with cold storage hearts, perfused heart function curves showed superior recovery of cardiac output (P = .001), power (P = .001), and efficiency (0.046 ± 0.01 vs 0.004 ± 0.003 joules/mL O2, P = .034). Myocardial adenosine triphosphate content (mmol/mg protein) was reduced significantly from the normal level of 26.5 (15.9, 55.8) to 5.08 (0.50, 10.4) (P = .049) in cold storage hearts but not in perfused hearts. Over a period of 2 hours, lactate levels in the blood perfusate were significantly lower in the perfusion group than in the cold storage group (P < .05). CONCLUSIONS: Continuous hypothermic crystalloid perfusion provides myocardial preservation superior to cold storage for long-term heart preservation, with potential applicability to marginal and donation after circulatory death hearts.

Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy.

BACKGROUND: Antihypertensive medicines are to known to cause diverse disturbances to electrolyte homeostasis; however, their potential to affect zinc is less well known. The primary aim was to explore whether antihypertensive medicines have the potential to affect zinc status. METHODS: A review of electronic databases was undertaken. Full-length English language articles describing clinical trials involving antihypertensive medicines and reporting on zinc measurements were reviewed. RESULTS: Eight eligible studies were identified which involved the use of ACE inhibitors, thiazide diuretics, beta blockers, or ARB drugs of which five included a control group Studies used urinary zinc excretion, plasma zinc levels or erythrocyte zinc as key measures of zinc status. Studies reported increased urinary zinc losses for captopril (from 50 mg/day), enalapril (20 mg/day), losartan (50 mg/day), losartan (50 mg/day) together with hydrochlorothiazide (12.5 mg/day), captopril (75 mg/day) together with frusemide (40 mg/day) and stand-alone hydrochlorothiazide (25 mg/day). Serum levels of zinc decreased with captopril (50-150 mg/day), verapamil (240 mg/day), atenolol (50-150 mg/day) and the combination of losartan (50 mg/day) and hydrochlorothiazide (12.5 mg/day), eryrthrocyte levels decreased with use of valsartan (80 mg/day) and in some studies for captopril, but not for metoprolol (100 mg/day), atenolol (50-150 mg/day), verapamil (240 mg/day), doxazosin (4 mg/day) or amlodipine 10 mg/day). Major limitations were that most studies were small and did not report on dietary zinc intake. CONCLUSION: The available evidence suggests that use of ACE inhibitors and angiotensin 2 receptor antagonists or thiazide diuretics have the potential to reduce zinc levels in hypertensive patients. Additional research using larger participant numbers and accounting for dietary zinc intakes are required.

Veno-right ventricular cannulation reduces recirculation in extracorporeal membrane oxygenation.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation has several advantages over veno-arterial support for patients with severe reversible respiratory failure. However, recirculation can limit oxygen delivery as pump flow increases. This could be ameliorated by placing the return catheter in the right ventricle instead of the central veins. We compared recirculation in veno-right ventricular support with that in conventional veno-venous support and its relationship with pump flow. METHODS: Five greyhound dogs were sequentially cannulated percutaneously for both veno-venous and veno-right ventricular support. Recirculation was measured by comparing oxygen levels in the circuit drainage and return lines before and immediately after a sudden increase in circuit oxygenation at pump flows between 0.5 L/min and 4 L/min for both modalities. RESULTS: Recirculation was reduced in veno-right ventricular support compared with conventional veno-venous support at 4 L/min pump flow (8.4% versus 37.9%, p=0.0076) and increased less with increases in pump flow (2.9% per 1 L/min vs. 11.1% per 1 L/min, p<0.0001). CONCLUSIONS: Recirculation can be dramatically reduced by returning blood into the right ventricle, which improves oxygen delivery to the lungs and the systemic circulation. The design of specialized catheters may facilitate percutaneous ventricular cannulation, improve safety and further reduce recirculation.

In vivo validation of pulsatile flow and differential pressure estimation models in a left ventricular assist device.

Implantation of sensors to measure hemodynamic parameters such as pulsatile pump flow and differential pressure (head) in an implantable rotary pump (IRBP) requires regular in situ calibration due to measurement drift. In addition, risks associated with sensor failure and thrombus formation makes the long-term implantation in patients problematic. In our laboratory, two stable and novel dynamical models for non-invasive pulsatile flow and head estimation were proposed and tested in vitro using mock circulatory loop experiments with varying hematocrit (HCT). Noninvasive measurements of power and pump speed were used as inputs to the flow model while the estimated flow was used together with the pump rotational speed as inputs to the head estimation model. In this paper, we evaluated the performance of the proposed models using in vivo experimental data obtained from greyhound dogs (N=5). Linear regression analysis between estimated and measured pulsatile flows resulted in a highly significant correlation (R(2) = 0.946) and mean absolute error (e) of 0.810 L/min, while for head, R(2) = 0.951 and e = 10.13 mmHg were obtained.

Focal cerebral oxygenation and neurological outcome with or without brain tissue oxygen-guided therapy in patients with traumatic brain injury.

BACKGROUND: In patients with severe traumatic brain injury (TBI), the depth and duration of cerebral hypoxia are independent predictors of outcome. This study aimed to evaluate the efficacy of brain oxygen-guided therapy in improving cerebral oxygenation and neurological outcome in severe TBI patients. METHODS: Thirty TBI patients had brain oxygen monitors placed contralateral to the side of mass lesions, or to the non-dominant side if injury was diffuse. The first 10 patients (Group 1, observational) had brain tissue oxygen (PbrO2) monitored, but not treated. The next 20 patients (Group 2, interventional) were treated according to brain tissue oxygen-guided algorithms aiming to improve cerebral oxygen availability. The 6-month neurological outcome of Group 2 patients was compared with that of Group 1 patients and with contemporary control patients (Group 3) treated without the use of brain oxygen monitoring. FINDINGS: The mean duration of brain hypoxic episodes (PbrO2 <15 mmHg) was 106 minutes in Group 1, and 34 minutes in Group 2 (p=0.01). Brain tissue oxygen was <15 mmHg for 10% of monitoring time in Group 1 and 2.8% in Group 2 (p=0.12). The peak incidence of cerebral hypoxic events in both groups occurred during post-injury day 5. The mean Injury Severity Score (ISS) of patients experiencing cerebral hypoxia was higher than that of patients without cerebral hypoxic episodes (33.7 vs 24.2, p=0.04). There was no statistically significant difference in neurological outcome between those patients treated with and those without brain oxygen-guided therapy. CONCLUSIONS: In TBI patients, brain tissue oxygen-guided therapy is associated with decreased duration of episodes of cerebral hypoxia. Larger studies are indicated to determine the effects of this therapy on neurological outcome.

Early lung transplantation success utilizing controlled donation after cardiac death donors.

Donation-after cardiac death (DCD) donor organs have potential to significantly alleviate the shortage of transplantable lungs. However, only limited data so far describes DCD lung transplantation (LTx) techniques and results. This study aims to describe the Alfred Hospital's early and intermediate outcomes following DCD donor LTx. Following careful experimentation and consultation DCD guidelines were created to utilize Maastricht category III lung donors from either the ICU or operating room(OR), with a warm ischemic time(WIT) of <60 min. Between May 2006 and December 2007, 22 referred DCD donors led to 11 attempted retrievals after withdrawal, resulting in 8 actual bilateral LTx (2 donors did not arrest in prescribed period and 1 donor had nonacceptable lungs). ICU WIT = 38.4 min (range 20-54, OR WIT = 12.7 min (11-15), p < 0.05. Post-LTx, 1 pulmonary hypertensive patient required ECMO for PGD3. The mean group pO2/FiO2 ratio at 24 hours was 307.7 (240-507) with an ICU stay of 9.5 days (2-21) and ward stay of 21.5 days (11-76). All 8 survive at a mean of 311 days (10-573) with good performance status and lung function. In conclusion, the use of Maastricht category III lungs for human LTx is associated with acceptable early clinical outcomes.

Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials.

Our objective was to review all published trials of coenzyme Q10 for hypertension, assess overall efficacy and consistency of therapeutic action and side effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study and eight open label studies. In the randomized controlled trials (n=120), systolic blood pressure in the treatment group was 167.7 (95% confidence interval, CI: 163.7-171.1) mm Hg before, and 151.1 (147.1-155.1) mm Hg after treatment, a decrease of 16.6 (12.6-20.6, P<0.001) mm Hg, with no significant change in the placebo group. Diastolic blood pressure in the treatment group was 103 (101-105) mm Hg before, and 94.8 (92.8-96.8) mm Hg after treatment, a decrease of 8.2 (6.2-10.2, P<0.001) mm Hg, with no significant change in the placebo group. In the crossover study (n=18), systolic blood pressure decreased by 11 mm Hg and diastolic blood pressure by 8 mm Hg (P<0.001) with no significant change with placebo. In the open label studies (n=214), mean systolic blood pressure was 162 (158.4-165.7) mm Hg before, and 148.6 (145-152.2) mm Hg after treatment, a decrease of 13.5 (9.8-17.1, P<0.001) mm Hg. Mean diastolic blood pressure was 97.1 (95.2-99.1) mm Hg before, and 86.8 (84.9-88.8) mm Hg after treatment, a decrease of 10.3 (8.4-12.3, P<0.001) mm Hg. We conclude that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects.

Artificial aortic valves: an overview.

This review discusses strategies that may address some of the limitations associated with replacing diseased or dysfunctional aortic valves with mechanical or tissue valves. These limitations range from structural failure and thromboembolic complications associated with mechanical valves to a limited durability and calcification with tissue valves. In pediatric patients there is an issue with the inability of substitutes to grow with the recipient. The emerging science of tissue engineering potentially provides an attractive alternative by creating viable tissue structures based on a resorbable scaffold. Morphometrically precise, biodegradable polymer scaffolds may be fabricated from data obtained from scans of natural valves by rapid prototyping technologies such as fused deposition modelling. The scaffold provides a mechanical profile until seeded cells produce their own extra cellular matrix. The microstructure of the forming tissue may be aligned into predetermined spatial orientations via fluid transduction in a bioreactor. Although there are many technical obstacles that must be overcome before tissue engineered heart valves are introduced into routine surgical practice these valves have the potential to overcome many of the shortcomings of current heart valve substitutes.

Similar therapeutic serum levels attained with emulsified and oil-based preparations of coenzyme Q10.

Studies of the therapeutic efficacy of coenzyme Q10 (CoQ10) have been confounded by the variable bioavailability of numerous CoQ10 preparations. The aims of the present study were to determine the early serum levels attained by two different preparations of CoQ10, a soybean oil-based preparation and a complex micelle emulsion and to assess whether these preparations of oral CoQ10 influence plasma lipid profiles. Twelve healthy individuals received 300 mg CoQ10 daily of either preparation for 7 days in a double-blind cross-over design with a 21-day washout period. Blood samples to determine serum levels of CoQ10 and lipids were taken at baseline, after 24 h and 7 days. Both preparations induced significant increases in serum CoQ10 levels at 24 h and 7 days. These were for soy oil: baseline 0.27 +/- 0.03 mol/L, 24 h 0.50 +/- 0.04 mol/L (180%) and 7 days 0.80 +/- 0.05 mol/L (291%), mean +/- SEM: for emulsion: baseline 0.29 +/- 0.03 mol/L, 24 h 0.45 +/- 0.03 mol/L (150%) and 7 days 0.79 +/- 0.06 mol/L (270%). There were no significant differences between CoQ10 levels for the two preparations at either time point. There was no change in any of the serum lipids following the 7 days treatment. We conclude that administration of either a soy oil suspension or a complex emulsion of CoQ10 increases serum levels to the therapeutic range within 1 week.

Quantification of mitochondrial DNA in peripheral blood mononuclear cells and subcutaneous fat using real-time polymerase chain reaction.

BACKGROUND: With decreased rates of HIV mortality and disease progression attributable to treatment with nucleoside analogue reverse transcriptase inhibitors (NRTIs), attention has now become focused on the toxicities of these forms of treatment. It is believed NRTIs cause a decrease in mitochondrial DNA (mtDNA) synthesis due to their inhibition of DNA polymerase gamma. This hypothesis is supported by in vitro data from muscle biopsies and human lymphoblastic cell lines. The resulting mitochondrial toxicity is thought to manifest itself in a variety of clinical symptoms including fatigue, fat wasting and peripheral neuropathy. A non-invasive test of mitochondrial toxicity is needed to assess toxicity and optimise HIV treatment strategies. Peripheral blood mononuclear cells (PBMC) and subcutaneous fat could be ideal and accessible sources of mtDNA for examining toxicity. OBJECTIVES: The objectives of this study were (a) to develop an assay to quantify the mtDNA copy number of PBMC and obtain reproducible results and (b) to establish the utility of subcutaneous fat as a source of mtDNA for quantification. STUDY DESIGN: PBMC were isolated from blood by centrifugation over Ficoll-Paque and subcutaneous fat was obtained from two 3 mm punch skin biopsies. Following DNA extraction, the mtDNA copy number in each sample was quantified by real-time polymerase chain reaction (PCR). RESULTS: The real-time PCR assay was found to generate consistent and reproducible results with replicates of samples undertaken within the same run, and in two or more different runs, having a mean coefficient of variation of 11.3 and 17.2%, respectively. PBMC and subcutaneous fat contained 409+/-148 and 2042+/-391 copies of mtDNA per cell, respectively. CONCLUSIONS: From the work carried out it can be concluded that firstly, the real-time PCR assay generates consistent and reproducible results, and secondly that mtDNA can be extracted and quantified from PBMC and subcutaneous fat.

Developing performance indicators for cardiac surgery: a demonstration project in Victoria.

Six Victorian cardiac surgical units pooled data in order to undertake a demonstration project aimed at developing performance indicators to assess outcomes following cardiac surgery. The outcome of the project was an indicative report for the purpose of monitoring surgical performance indicators in a format suitable for: (i) the general public; (ii) the Victorian State Government; and (iii) the participating units and surgeons. Each participating cardiac surgical unit had an existing database used for recording information from each procedure. A request was made to each unit to extract a subset of data from all cases entered over the past 5 years. The proposed list of performance indicators included surgical mortality (within the period of admission for surgery), complication rates (including sternal infection, postoperative myocardial infarction, postoperative stroke, haemorrhage requiring return to theatre), and length of hospital stay. A model was developed from the data and used to provide risk-adjusted measures of hospital performance. Cases from five cardiac surgical units (n = 10 715) were included in the final analysis. A risk-adjusted model (including age, sex, diabetes, hypertension, smoking, procedure type, urgency of procedure) was developed for surgical mortality. Performance indicators for coronary artery bypass graft surgery, including mortality, sternal infection rate and length of hospital stay are presented. From the available data, performance indicators for cardiac surgery in Victorian hospitals compared favourably with international benchmarks. This project has demonstrated that prospective data collection using a standardised system could readily produce local risk-adjustment models for cardiac surgery to aid in developing appropriate performance indicators.

Cardioplegic strategies for calcium control: low Ca(2+), high Mg(2+), citrate, or Na(+)/H(+) exchange inhibitor HOE-642.

BACKGROUND: Ca(2+) overload plays an important role in the pathogenesis of cardioplegic ischemia-reperfusion injury. The standard technique to control Ca(2+) overload has been to reduce Ca(2+) in the cardioplegic solution (CP). Recent reports suggest that Na(+)/H(+) exchange inhibitors can also prevent Ca(2+) overload. We compared 4 crystalloid CPs that might minimize Ca(2+) overload in comparison with standard Mg(2+)-containing CP: (1) low Ca(2+) CP (0.25 mmol/L), (2) citrate CP/normal Mg(2+) (1 mmol/L Mg(2+)), (3) citrate CP/high Mg(2+) (9 mmol/L Mg(2+)), and (4) the addition of the Na(+)/H(+) exchange inhibitor HOE-642 (Cariporide). We also tested the effect of citrate titration in vitro on the level of free Ca(2+) and Mg(2+) in CPs. METHODS AND RESULTS: Isolated working rat heart preparations were perfused with oxygenated Krebs-Henseleit buffer and subjected to 60 minutes of 37 degrees C arrest and reperfusion with CPs with different Ca(2+) concentrations. Cardiac performance, including aortic flow (AF), was measured before and after ischemia. Myocardial high-energy phosphates were measured after reperfusion. The in vitro addition of citrate to CP (2%, 21 mmol/L) produced parallel reductions in Mg(2+) and Ca(2+). Because only Ca(2+) was required to be low, the further addition of Mg(2+) increased free Mg(2+), but the highest level achieved was 9 mmol/L. Citrate CP significantly impaired postischemic function (AF 58.3+/-2. 5% without citrate versus 41.6+/-3% for citrate with normal Mg(2+), P:<0.05, versus 22.4+/-6.2% for citrate with high Mg(2+), P:<0.05). Low-Ca(2+) CP (0.25 mmol/L Ca(2+)) significantly improved the recovery of postischemic function in comparison with standard CP (1.0 mmol/L Ca(2+)) (AF 47.6+/-1.7% versus 58.3+/-2.5%, P:<0.05). The addition of HOE-642 (1 micromol/L) to CP significantly improved postischemia function (47.6+/-1.7% without HOE-642 versus 62.4+/-1. 7% with HOE-642, P:<0.05). Postischemia cardiac high-energy phosphate levels were unaffected by Ca(2+) manipulation. CONCLUSIONS: (1) A lowered Ca(2+) concentration in CP is beneficial in Mg(2+)-containing cardioplegia. (2) The use of citrate to chelate Ca(2+) is detrimental in the crystalloid-perfused isolated working rat heart, especially with high Mg(2+). (3) The mechanism of citrate action is complex, and its use limits precise simultaneous control of Ca(2+) and Mg(2+). (4) HOE-642 in CP is as efficacious in preservation of the ischemic myocardium as is the direct reduction in Ca(2+).

Tolerance to ischemia and hypoxia is reduced in aged human myocardium.

BACKGROUND: Recovery of cardiac function after cardiac surgery and other interventional cardiac procedures in elderly patients is inferior to that in younger patients, suggesting that the aged myocardium is more sensitive to ischemia and other stresses. Although convincing data from animal studies of senescence now exist, there is a dearth of controlled in vitro studies that examine the specific response of aged human myocardium to the stress of hypoxia or ischemia. OBJECTIVE: We sought to determine the effect of age on the capacity of human atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. METHODS: Atrial pectinate trabeculae were dissected from the tip of 58 right atrial appendages harvested during an operation in patients aged between 34 and 89 years and electrically stimulated at 1 Hz in oxygenated Ringer's solution at 37 degrees C. Tissues experienced 30 minutes of either hypoxia (N(2) and perfusate) or simulated ischemia (humidified N(2) without perfusate) and were returned to normoxia for recovery of function for 30 minutes. Developed force and other contractile variables were determined during each period. RESULTS: Under normoxic conditions, no significant age difference was observed for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced recovery of developed force (48.5% +/- 22.2% [n = 11] and 44.9% +/- 19% [n = 12], respectively) compared with that found (66.4% +/- 19.7% [n = 15]) in the younger (34-59 years) group (mean +/- SD, P =.02). Similarly, after simulated ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subjects showed reduced recovery of developed force (35.7% +/- 17% [n = 5] and 51.1% +/- 11.8% [n = 9], respectively) compared with that found (68.2% +/- 10.4% [n = 6]) in the group of 34- to 59-year-old subjects (P =.01). Multivariable analysis, comparing 20 factors of surgical patient characteristics and recovery of developed force, found that only age (P =.01) and hypertension (P =.01) were predictors of reduced recovery of developed force after either hypoxia or simulated ischemia. CONCLUSIONS: In aged human atrial myocardium, the capacity to recover contractile function after in vitro hypoxia or simulated ischemia is reduced compared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery.

A simplified method of harvesting and dilating the radial artery achieves acceptable clinical outcomes.

BACKGROUND: The recent successful revival of the radial artery as a coronary-bypass conduit has been attributed to a minimally traumatic harvesting technique without diathermy, combined with long-term oral calcium antagonist therapy. We describe a simplified technique of harvesting the radial artery, which reduces procurement time and maintains conduit relaxation. METHODS: Radial arteries were harvested using diathermy and topical glyceryl trinitrate-verapamil dilator solution. Postoperatively, intravenous glyceryl trinitrate, but no calcium antagonist was used. The clinical results in the first 100 consecutive patients receiving radial artery grafts (RA group), procured using this technique, were compared with a group of 100 patients receiving saphenous vein conduits (SV group) immediately prior to the introduction of the radial artery at our institution. RESULTS: There were no demographic differences between the two groups, other than the SV group being slightly older. There was one intraoperative death in each group. There was no difference in the rate of peri-operative myocardial infarction or length of stay in the intensive care unit. At a median follow-up time of 16 months for the RA group, and 25 months for the SV group, the survival rates were 97 and 94%, respectively. All survivors were in the New York Heart Association class I. In the SV group, two postoperative angioplasties were performed. CONCLUSIONS: These early results suggest that this method of procuring the radial artery using diathermy, glyceryl trinitrate and no postoperative calcium antagonists, is rapid, safe and effective. The continued use of this technique is justified, while awaiting the results of long-term angiographic studies.

Outcomes of coronary artery bypass grafting: a 3 year analysis using the Society of Thoracic Surgeons Database.

BACKGROUND: Accurate risk factor analysis is a critical element in contemporary cardiac surgical practice. In the USA, the Society of Thoracic Surgeons Database allows institutions and individual surgeons to carry out detailed patient risk assessment and to review their cardiac surgical outcomes in a comparative fashion. METHODS: To evaluate outcomes of isolated coronary artery bypass grafting, data from all patients operated upon at the Alfred Hospital, Melbourne, Australia, over a 3 year period were entered into the Society of Thoracic Surgeons Database. RESULTS: Our results (mortality and morbidity) compared favourably with those contained within this large international database. CONCLUSION: It is hoped that a similar Australasian database can be established to facilitate a meaningful local risk assessment and a comparative analysis of outcomes of cardiac surgical procedures.