Ruchong Ou

Coenzyme Q10 Protects the Aging Heart against Stress

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.

Oxidative Stress in Surgery in an Ageing Population : Pathophysiology and Therapy

Reactive oxygen species (ROS) play an important role in the regulation of normal cellular function. When ROS are produced in excess they can have detrimental effects, a state known as oxidative stress. Thus ROS play both physiological and pathophysiological roles in the body. In clinical practice oxidative stress and its counterpart, antioxidant capacity can be measured and can guide remedial therapy. Oxidative stress can have a negative impact in all forms of major surgery including cardiac surgery, general surgery, trauma surgery, orthopedic surgery and plastic surgery; this is particularly marked in an ageing population. Many different therapies to reduce oxidative stress in surgery have been tried with variable results. We conclude that in surgical patients the assessment of oxidative stress, improvement of the understanding of its role, both positive and negative, and devising appropriate therapies represent fruitful fields for future research.

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

Abstractyounger 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.

Twelve-hour reanimation of a human heart following donation after circulatory death.

Despite increasing use of donation after cardiac death (DCD) and encouraging results for non-cardiac transplants, DCD cardiac transplantation has not been widely adopted because, (1) the DCD heart sustains warm ischaemic injury during the death process and (2) conventional static cold storage significantly adds to the ischaemic injury. We have developed a simple system for perfusion of the DCD heart with cold crystalloid solution using gravity-feed that can reduce ischaemic injury and potentially render the heart suitable for transplantation. This report describes the first application of this technique to a human DCD heart with good functional metabolic recovery over 12h on an ex vivo rig.

A novel combination technique of cold crystalloid perfusion but not cold storage facilitates transplantation of canine hearts donated after circulatory death

BACKGROUND Donation after circulatory death (DCD) represents a potential new source of hearts to increase the donor pool. We showed previously that DCD hearts in Greyhound dogs could be resuscitated and preserved by continuous cold crystalloid perfusion but not by cold static storage and could demonstrate excellent contractile and metabolic function on an in vitro system. In the current study, we demonstrate that resuscitated DCD hearts are transplantable. METHODS Donor Greyhound dogs (n = 12) were divided into perfusion (n = 8) and cold static storage (n = 4) groups. General anesthesia was induced and ventilation ceased for 30 minutes to achieve circulatory death. Donor cardiectomy was performed, and for 4 hours the heart was preserved by controlled reperfusion, followed by continuous cold perfusion with an oxygenated crystalloid perfusate or by static cold storage, after which orthotopic heart transplantation was performed. Recovery was assessed over 4 hours by hemodynamic monitoring. RESULTS During cold perfusion, hearts showed continuous oxygen consumption and low lactate levels, indicating aerobic metabolism. The 8 dogs in the perfusion group were weaned off bypass, and 4 hours after bypass produced cardiac output of 4.73 ± 0.51 liters/min, left ventricular power of 7.63 ± 1.32 J/s, right ventricular power of 1.40 ± 0.43 J/s, and left ventricular fractional area shortening of 39.1% ± 5.2%, all comparable to pre-transplant values. In the cold storage group, 3 of 4 animals could not be weaned from cardiopulmonary bypass, and the fourth exhibited low-level function. CONCLUSIONS Cold crystalloid perfusion, but not cold static storage, can resuscitate and preserve the DCD donor heart in a canine model of heart transplantation, thus rendering it transplantable. Controlled reperfusion and cold crystalloid perfusion have potential for clinical application in DCD transplantation.

Age-related decline in stress responses of human myocardium may not be explained by changes in mtDNA

Elderly patients undergoing cardiac surgery are more likely to suffer postoperative heart failure than younger patients. This phenomenon is mirrored by an age-related loss of mitochondrial function and by an in vitro loss of myocardial contractile force following a stress. To examine the possibility that loss of mtDNA integrity may be responsible, we quantified representative age-associated mtDNA mutations (mtDNA(4977) and mtDNA(A3243G)) and mtDNA copy number using quantitative polymerase chain reaction in atrial samples obtained during cardiac surgery. The myocardium underwent organ bath contractility testing before and after either an ischaemic or hypoxic stress. We found that with age, recovery of developed force after either stressor significantly declined (p<0.0001). The abundance of mtDNA(4977) correlated weakly with loss of contractility (R(2)=0.09, p=0.047). However, the abundance level was low (average 0.0075% of total mtDNA) and the correlation disappeared when age was included in a multivariate analysis. Neither the abundance of mtDNA(A3243G) nor mtDNA copy number correlated with reduced recovery of developed force after stress. We conclude that, although mtDNA mutations (as exemplified by mtDNA(4977)) accumulate in the ageing heart, they are unlikely to make a major contribution to loss of contractile function.

Prevalence of zinc deficiency in cardiac surgery patients

BACKGROUND The aim of this study was to define the status of preoperative zinc levels in patients with heart disease presenting for cardiac surgery and to identify any predictors for and any clinical consequences of low zinc levels. METHODS Adult patients presenting for elective surgery, either coronary artery bypass graft surgery and/or valve replacement, provided a fasting blood sample on the day of admission for surgery. Plasma and erythrocyte zinc levels were analysed and the levels correlated with the patients characteristics and clinical outcomes. RESULTS Of 56 patients 53% (n=30) had abnormally low plasma zinc levels (<12μmol/L) and 5.5% (n=3) had abnormally low erythrocyte zinc levels (<160μmol/L), indicative of deficiency. There were significant associations between lower plasma zinc levels and the presence of hypertension (p=0.02), hypercholesteraemia (p=0.02) and higher body mass index (BMI) (p=0.034) but no effect on major postoperative clinical outcomes. CONCLUSIONS This small study shows that zinc deficiency is common in cardiac surgery patients, especially in the presence of hypertension, hypercholesterolaemia or obesity. The effects of zinc deficiency in cardiac surgery need to be further investigated.

In Vivo Validation of Irreversible Electroporation Electric Field Threshold for Prostate Tissue

Irreversible electroporation (IRE) is a non-thermal focal ablation technique that uses needle electrodes to deliver a series of brief (100μs duration) electric pulses into the targeted region. These alter cellular transmembrane potentials, destabilizing the membranes in a manner that kills the cells while sparing major vasculature and other sensitive structures. IRE can therefore be used in regions ineligible for surgical resection or thermal ablation. Treatments result in rapid lesion creation and resolution [1], are unaffected by the blood perfusion “heat sink”, can be planned with numerical modeling [2], and its effects can be readily monitored with various imaging modalities [3]. Therapeutic ire has proven effective in the treatment of experimental [4] and clinical tumors. A human safety study attained complete regression in 46 of 69 tumors ineligible or unresponsive to conventional treatment [5], and veterinary case studies convey its utility in large difficult tumors [6, 7].Copyright