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Biomedical subjects

S F Bolling

Publications and source records attributed to S F Bolling.

At least 19 recordsLinked to original sources

Bedside chest radiography as part of a postcardiac surgery critical care pathway: a means of decreasing utilization without adverse clinical impact.

OBJECTIVE: To evaluate the use of bedside chest radiography and patient outcome before and after implementation of a cardiac surgery critical care pathway that included guidelines for bedside radiography. DESIGN: A cohort observational study. SETTING: A university hospital in the midwest. PATIENTS: Three groups, of 100 patients each, undergoing cardiac surgery in 1990, 1991, and 1995. INTERVENTION: Introduction of a critical care pathway. MEASUREMENTS: Medical records were retrospectively reviewed in three groups of 100 patients each: before the introduction of the critical care pathway; 2 months after introduction of the pathway in 1991; and 4 yrs after introduction in 1995. Data were analyzed to determine operative risk for each group. Subsequent analyses determined bedside radiography use, total length of hospital stay, and patient outcome (mortality rate, complications requiring intervention, and reoperation) during hospitalization and at outpatient follow-up 15-30 days postdischarge. RESULTS: Total length of hospital stay was shorter for the 1995 group (7.6+/-6.6 days) compared with other groups (prepathway, 11.1+/-10.3 days; 1991 postpathway, 10.2+/-9.6 days; p<.05). The mean numbers of radiographs per patient were as follows: prepathway, 5.1; 1991 postpathway, 5.2; and 1995 postpathway, 3.3. The mean number of radiographs in the 1995 group was significantly lower (p = .02). More patients had the proposed number of two bedside radiographs described in the pathway in the 1995 group compared with the other groups (prepathway, p<.0001; the two-month postpathway group, p = .01). Twenty-three malpositioned catheters/tubes were found in the prepathway and 1991 groups compared with 11 in the 1995 group (p = .02). No statistically significant difference was found in inpatient complications (mediastinal bleeding, pneumothoraces, and pleural effusions), postdischarge complications, reoperations, or mortality rate. CONCLUSION: Introduction of a critical care pathway can decrease the use of bedside radiography without adversely affecting near-term patient outcomes.

Adult

RSR13, a synthetic allosteric modifier of hemoglobin, improves myocardial recovery following hypothermic cardiopulmonary bypass.

BACKGROUND: During hypothermic blood cardioplegia, oxygen delivery to myocytes is minimal with ineffective anaerobic metabolism predominating. RSR13, 2-[4-[[(3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylpropionic acid, a synthetic allosteric modifier of hemoglobin (Hb), increases release of oxygen from Hb, increasing oxygen availability to hypoxic tissues, and reverses the hypothermia-dependent increase in Hb oxygen affinity. We studied recovery of myocardial mechanical and metabolic function and examined myocardial morphology after cardioplegia, comparing RSR13 (1.75 mmol/L)-supplemented blood (RSR13-BC) to standard blood cardioplegia (BC). METHODS AND RESULTS: Twelve dogs underwent 15 minutes of 37 degrees C global ischemia on cardiopulmonary bypass, followed by 75 minutes of hypothermic cardioplegia (13 degrees C) with either BC (n=6) or RSR13-BC (n=6). There were no differences in baseline function between groups. Cardiac function was assessed after 30 minutes of 37 degrees C reperfusion (BC versus RSR13-BC, respectively) by measuring: % return to normal sinus rhythm (0/100%), % of baseline+dP/dt (33.7+/-1.7/76.3+/-1.9), % of baseline-dP/dt (26.6+/-2.0/81.1+/-1.6), stroke volume (3.5+/-0.5/7.1+/-0.9 mL), cardiac output (340+/-20/880+/-40.3 mL/min), and LVEDP (11.3+/-2.2/0. 3+/-2.9 mm Hg). Postischemic oxidative and metabolic parameters including myocardial lactate, pyruvate, ATP content, and percent water content also were determined. Histological analysis demonstrated preservation of endothelial and myocyte morphology in hearts receiving RSR13-BC compared with BC. CONCLUSIONS: These results indicate that in the setting of hypothermic cardiopulmonary bypass, RSR13 improves recovery of myocardial mechanical and metabolic function compared with standard hypothermic BC. Findings from this study suggest that RSR13-BC, by decreasing hemoglobin oxygen affinity, improves oxidative metabolism and preserves cellular morphology, resulting in significantly improved contractile recovery on reperfusion.

Allosteric Regulation

Opiate drugs and delta-receptor-mediated myocardial protection.

BACKGROUND: Hypothermic myocardial arrest is necessary to complete most cardiac surgery, which limits the success of such operations. Similarly, cold, inhospitable environments limit the survival of warm-blooded animals. Animals have successfully adapted to this challenge through hibernation. Hibernation is an energy-conserving state, now known to be governed by cyclical variation in endogenous opiate compounds. It may also be induced in nonhibernators via hibernating animal serum factors or delta-opiate peptides. Furthermore, hibernation-induction triggers extend organ preservation in many models. This study examined whether opiate drugs with an affinity for the delta-opiate receptor confer similar protection. METHODS AND RESULTS: Isolated hearts harvested from New Zealand White rabbits were treated with either cardioplegia alone or delta-opiate drugs (fentanyl, morphine, buprenorphine, pentazocine) followed by 2 hours of 34 degrees C ischemia. Hearts were then reperfused, and functional and metabolic indices of treated groups were compared with untreated controls. Isovolumic developed pressure, coronary flow, and oxygen consumption were compared as a percent of preischemia versus 45 minutes after reflow. Developed pressure and oxygen consumption were better preserved in the morphine, buprenorphine, and pentazocine groups when compared with cardioplegia alone. CONCLUSIONS: Drugs with delta-opiate activity confer myocardial protection, which is additive to cardioplegia. Use of delta-opiate drugs in this context may have important clinical implications.

Analgesics, Opioid

Anti-TNF antibody modulates cytokine and MHC expression in cardiac allografts.

Tumor necrosis factor-alpha (TNF) is a multifunctional cytokine evoked in response to alloantigen stimulation and may be involved in lymphocyte activation, adhesion molecule expression, and regulation of MHC class II antigens. Anti-TNF treatment prolongs cardiac allograft survival. We investigated the role of anti-TNF in the regulation of MHC class II antigens and cytokine mRNA expression of TNF, interferon-gamma (IFN), IL-2, IL-4, and IL-10 in cardiac allografts to elucidate its immunological mechanism. These in vivo studies were conducted using a rat MHC mismatch Brown-Norway to Lewis (BN to LEW) heterotopic cardiac transplant model. In control untreated rats, allografts were rejected at 6.8 +/- 0.6 days. Allograft survival was significantly prolonged to 12.7 +/- 1.4 days with anti-TNF treatment. MHC class II expression, analyzed by indirect immunofluorescence cytometry, demonstrated that MHC class II-positive cells increased by 25% in spleens of untreated allografted rats compared to naive rats, while anti-TNF-treated allografted rats had a similar percentage of MHC II cells as naives. Further, naive, untransplanted rats and both anti-TNF and untreated, transplanted rats had heart and spleens harvested on Day 5 post-transplant. Cytokine mRNA expression was determined by semiquantitative RT-PCR. In heart and spleen cells from naives, TNF mRNA expression was undetectable or very weak. However, in rejecting allografts and spleen cells from untreated recipients, TNF expression was remarkably increased, while anti-TNF attenuated this TNF expression in both heart graft and spleen cells. Furthermore, IL-2, IL-10, and IFN expression were absent in naive hearts. However, in untreated allografts IL-2, IL-10, and IFN were strongly expressed, which was markedly decreased after anti-TNF treatment. Finally, IL-4 expression was found equally in naive hearts, untreated allografts, and anti-TNF-treated allografts. These results suggest that anti-TNF antibody treatment may not only neutralize TNF activity but also play a role in altering cytokine mRNA expression and MHC class II expression.

Animals

Increased rat cardiac allograft survival by the glycosaminoglycan pentosan polysulfate.

BACKGROUND: Modulation of the inflammatory response has proven to be of benefit in salvaging cardiac allografts at risk of irreversible injury. Pentosan polysulfate (PPS), like heparin, is a negatively charged sulfated glycosaminoglycan (GAG) that possesses anti-inflammatory properties including the ability to inhibit activation of the complement system. This study was conducted to determine the potential of PPS to prolong allograft survival in an experimental model of cardiac transplantation. MATERIALS AND METHODS: A heterotopic cardiac transplant was performed by implanting the heart from fetal Brown Norway rats into the ear pinnae of adult Lewis rats. Vehicle (saline) or PPS (30 mg/kg) was administered subcutaneously immediately after transplantation and daily thereafter (n = 6 in each group). Another GAG, heparin, was also analyzed to determine the effect of anticoagulation on transplant survival (n = 6). RESULTS: Treatment with PPS significantly (P < 0. 05) increased allograft survival time as compared to vehicle-treated animals (8.0 +/- 0.3 days vs 5.5 +/- 0.5 days). The results noted with PPS were similar to those observed in cyclosporine (10 mg/kg; n = 6)-treated animals (8.25 +/- 0.25 days). Treatment with heparin (300 U/kg/day) did not significantly prolong cardiac graft survival time, suggesting that anticoagulation is not sufficient to prolong transplant survival. Analysis of tissue histology showed diminished transplant rejection as evidenced by decreased white blood cell infiltration and cellular necrosis. CONCLUSIONS: The results of this study indicate that PPS possesses the ability to prolong cardiac transplant viability in a heterotopic cardiac transplant model, independent of its anticoagulant actions.

Animals

Delta opioid receptors and low temperature myocardial protection.

BACKGROUND: Cardiac surgery continues to be limited by an inability to achieve complete myocardial protection. This may result from the use of hypothermic cardioplegia. Interestingly, the subcellular changes of animal hibernation parallel the altered biology of induced hypothermic myocardial ischemia, but are well tolerated by hibernated mammalian myocardium. Evidence indicates this protection is mediated by activation of the delta opioid receptor, which elicits profound metabolic effects at the whole animal, organ, and cell level. In this study, we sought to determine if pentazocine, with agonist activity at the delta opioid receptor, could improve myocardial recovery following global ischemia over a wide range of temperatures. METHODS: Isolated rabbit hearts received either standard cardioplegia or were pretreated with racemic, d or 1 isomer pentazocine. Hearts were then subjected to 2 hours at 34 degrees C, or 3.5 hours at 20 degrees C, or 4 hours at 10 degrees C of cardioplegic ischemia and reperfused. Functional recovery was compared to controls. RESULTS: Isovolumic developed pressure, coronary flow, oxygen consumption, and ultrastructural preservation were enhanced with pentazocine delta opioid mediated protection, which appears to be additive to standard cardioplegia, even at low temperatures. CONCLUSIONS: Teleologically, delta opioid protection parallels animal hibernation, which occurs from 34 degrees down to 0 degrees C. The use of delta opioid receptor agonists may have important clinical implications for cardiac surgery and deserves further study.

Animals

The impact of new technology on a clinical practice.

The use of xenograft stentless tissue valves has increased because of excellent hemodynamics and availability. This article describes the impact of the incorporation of this new technology into a single institutional practice over time. A time span for continual usage of the new stentless Freestyle valve was divided into four distinct chronological groups and evaluated. Data on 266 consecutive patients receiving the Freestyle prosthesis were analyzed with regard to demographics, degree of illness, complexity of surgery, and outcomes to discover any distinct changes over time with respect to experience and acquired confidence and surgical expertise. Findings among the four groups were compared using Student's t-test. The only change in patient demographics was younger age (mean age decreased from 70 to 62 years). The number of procedures rose steadily, and the degree of illness increased as noted in the increase between groups in the percentage of patients with comorbidities (from 45% to 92%). The complexity of surgery score steadily increased (from 1.9 to 2.5); however, the mean cross-clamp time did not change. The surgical mortality rate for the entire study was 3.4%. In group 1, the mortality was 7.5% but decreased rapidly and remained steady throughout the rest of the study. The use of the Freestyle stentless conduit in a single practice over time shows a distinct learning curve. With experience, valves are placed in younger, sicker patients who require more complex surgery. Surgical outcomes and efficiency improve with acquired surgical expertise.

Adult

Hibernation triggers and myocardial protection.

BACKGROUND: Hypothermic cardioplegia provides myocellular protection, yet postischemic dysfunction remains a significant problem. Interestingly, the subcellular changes in hibernation parallel the altered biology of induced cardiac ischemia but are well tolerated by hibernated mammalian myocardium. An uncharacterized factor derived from hibernating animals, hibernation induction trigger (HIT), has been shown to induce hibernation in active animals and afford myocardial protection after ischemia-reperfusion injury. Therefore, it was of interest to further characterize the cardioprotective effects of HIT in the setting of ischemia-reperfusion injury. METHODS AND RESULTS: To determine whether HIT could improve myocardial recovery after global ischemia, isolated rabbit hearts received either standard cardioplegia or HIT in the cardioplegia or underwent preperfusion with HIT before cardioplegia. Alternatively, to determine whether HIT requires metabolic alteration, additional rabbits had in vivo pretreatment with HIT from 15 minutes to 5 days before ischemia. All hearts underwent 2 hours of global ischemia at 34 degrees C. Recovery of postischemic isovolumic developed pressure, coronary flows, and MVO2 were compared. Compared with vehicle pretreatment, HIT pretreatment (1 hour) significantly enhanced indexes of functional recovery, including developed pressure (38 +/- 3 versus 69 +/- 7 mm Hg) and coronary flow (46 +/- 2 versus 82 +/- 11 mL/min). In addition, ultrastructural morphology was preserved but only with in vivo pretreatment. Liver protein content was not increased in rabbits treated from 12 hours to 5 days with HIT versus controls, belying a protein neosynthesis mechanism. However, the temporal sequences suggested conversion of an inactive HIT profactor to an active form. CONCLUSIONS: Administration of serum derived from hibernating black bears to rabbits affords protection against ischemia-reperfusion injury compared with vehicle (saline)-treated animals in a rabbit isolated heart preparation. It is apparent that HIT deserves further identification and mechanistic study in the setting of ischemia-reperfusion injury.

Animals

Temperature threshold and modulation of energy metabolism in the cardioplegic arrested rabbit heart.

Hypothermia protects ischemic tissues by reducing ATP utilization and accumulation of harmful metabolites. However, it also reduces ATP production, which might cause deterioration in the energy supply/demand ratio. Modulation of energy supply/demand according to temperature has not been previously studied in detail. In this study, isolated, perfused rabbit hearts (n = 60) were used to determine the effects of various temperatures on myocardial energy metabolism and function during cardioplegic arrest. Ischemia was induced by crystalloid cardioplegic solution at 4, 18, 30, and 34 degrees C for 120 min, respectively. At each temperature, the hearts were divided into a glucose-treated group which contained 22 mM glucose in cardioplegic solution as the only substrate and a control group which contained 22 mM mannitol to keep same osmolarity. Following 15 min reperfusion, recovery of left ventricular developed pressure (DP), +/- dP/dtmax, and the product of heart rate and DP were significantly higher in 30, 18, and 4 degrees C groups than those in 34 degrees C control group. The functional recovery was also significantly higher in the 34 degrees C glucose-treated group than that in the 34 degrees C control group, but there was no difference between those groups at 30 degrees C and the temperature below 30 degrees C. Myocardial ATP concentration was significantly lower in 34 degrees C control group than those in other groups. There is a close relationship between myocardial ATP concentration and functional recovery (R2 = 0.90). The accumulations of lactate and CO2 were significantly higher at 34 degrees C in glucose-treated group than those in the control group. However, there was no significant difference between these two groups at 30 degrees C and the temperature below 30 degrees C. These results indicate that under these study conditions: (1) a marked decrease in energy supply/demand occurs above 30 degrees C, implying that a temperature threshold exists; and (2) this can be ameliorated by provision of glucose as substrate in cardioplegia solution.

Adenosine Triphosphate

Postischemic function and protein kinase C signal transduction.

BACKGROUND: The protective effects of myocardial preconditioning may occur by way of multiple mechanisms, with G-protein-mediated protein kinase C (PKC) translocation as a final common pathway. In this study we investigate the pharmacologic induction of preconditioning, by PKC translocation, using PKC agonists/antagonists to reveal its effects on contractile function after myocardial ischemia. METHODS: Langendorff-perfused rabbit hearts received: (1) control; (2) dimethyl sulfoxide (vehicle); (3) acetylcholine (0.55 mmol/L; PKC agonist); (4) 1,2-s,n-dioctanoylglycerol (DOG; 22 mmol/L; PKC agonist); (5) chelerythrine (0.8 mmol/L; PKC antagonist); or (6) DOG-chelerythrine followed by a 2-hour ischemic period, using modified St. Thomas cardioplegia and a 45-minute reperfusion period. The period of ischemia was chosen so as to allow for improvement by appropriate agonists. To observe metabolic changes, tissue nucleotides and nucleosides were measured. Membrane and cytosolic fractions of PKC were determined by an anti-PKC antibody directed against the PKC delta isozyme. Lactate levels and myocardial pH were measured. RESULTS: The PKC agonists DOG and acetylcholine showed the greatest recovery of developed pressure (68% +/- 2%, 60% +/- 9%, respectively). Although pH, lactate, and nucleotide levels were similar between groups at all times, myocyte PKC translocation demonstrated 25% of PKC delta isoforms on cell membrane sites during baseline, which shifted to 67% delta 17% with unprotected ischemia. DOG mimicked this shift with 58% delta 12% of PKC delta isoforms on membranes, which was also blocked by chelerythrine to 35% +/- 7%. CONCLUSIONS: These data demonstrate that PKC translocation results in improved postischemic function, not by alteration of energetics or metabolism, and deserves further investigation.

Acetylcholine

Combined lung volume reduction and mitral valve reconstruction.

Combined lung volume reduction and mitral valve reconstruction was performed in a 66-year-old man with end-stage emphysema and severe mitral regurgitation. Quality of life, pulmonary function, 6-minute walk, echocardiographic degree of mitral regurgitation, and New York Heart Association heart failure classification all improved substantially. A lung volume reduction operation can safely be combined with complex cardiac operations for patients with disabling dyspnea of a multifactorial nature.

Aged

Intermediate-term outcome of mitral reconstruction in cardiomyopathy.

OBJECTIVE: Severe mitral regurgitation is a frequent complication of end-stage cardiomyopathy that contributes to heart failure and predicts a poor survival. We studied the intermediate-term outcome of mitral reconstruction in 48 patients who had cardiomyopathy with severe mitral regurgitation and were operated on between June 1993 and June 1997. METHODS: Ages ranged from 33 to 79 years (63 +/- 6 years) with left ventricular ejection fractions of 8% to 25% (16% +/- 3%). All patients were receiving maximal drug therapy and were in New York Heart Association class III-IV with severe, refractory 4+ mitral regurgitation. Operatively, all 48 had undersized flexible annuloplasty rings inserted, 7 had coronary bypass grafts for incidental disease, 11 had prior bypass grafts, and 11 also had tricuspid valve repair. RESULTS: One operative death occurred as a result of right ventricular failure. Postoperative transesophageal echocardiography revealed mild mitral regurgitation in 7 patients and no mitral regurgitation in 41. There were 10 late deaths, 2 to 47 months after mitral reconstruction. The 1- and 2-year actuarial survivals have been 82% and 71%. At a mean follow-up of 22 months, the number of hospitalizations for heart failure has decreased, and 1 patient has had heart transplantation. Significantly, New York Heart Association class improved from 3.9 +/- 0.3 before the operation to 2.0 +/- 0.6 after the operation. Twenty-four months after the operation, left ventricular volume and sphericity have decreased, whereas ejection fraction and cardiac output have increased. CONCLUSION: Whether this favorable modification of left ventricular function and geometry will persist remains unknown. However, mitral repair for cardiomyopathy with mitral regurgitation allows new strategies for these patients.

Actuarial Analysis

Isolation and partial characterization of an opioid-like 88 kDa hibernation-related protein.

Previous studies show that infusion of hibernating woodchuck albumin (HWA) induces hibernation in summer-active ground squirrels and results in profound behavioral and physiological depression in primates. These effects are reversed by the administration of opiate antagonists, suggesting that the putative hibernation induction trigger (HIT) may act through opioid receptors. We have demonstrated that both HIT-containing plasma and the synthetic alpha opioid D-Ala2-D-Leu5-enkephalin (DADLE), which mimics the activity of HIT in hibernators, extend tissue survival time of a multi-organ autoperfusion system by 3-fold. In this study we present the first data showing biological activity with a much more highly purified plasma fraction from hibernating woodchucks, identified as the hibernation-related factor (HRF). Both the HRF and DADLE show opiate-like contractile inhibition in the mouse vas deferens (Mvd) bioassay. We also have preliminary evidence in an isolated rabbit heart preparation indicating that the HRF and DADLE act similarly to restore left ventricular function following global myocardial ischemia. Furthermore, we have partially sequenced an alpha 1-glycoprotein-like 88 kDa hibernation-related protein (p88 HRP) present in this fraction, which may prove to be the blood-borne HIT molecule.

Amino Acid Sequence

The role of private prayer in psychological recovery among midlife and aged patients following cardiac surgery.

Issues related to psychological recovery following coronary bypass surgeries (CABG) have emerged in recent years. Other research has shown the effects of spiritual or religious activities on health and aging. However, little is known about the relationship of spiritual coping, including religious coping, to post-CABG adjustment. This study addressed multifactorial determinants of postoperative psychological recovery and the effects of private prayer, a form of spiritual coping, on the recovery of 151 older patients. Results show that most patients pray about their postoperative problems and that private prayer appears to significantly decrease depression and general distress one year post-CABG.

Adaptation, Psychological

Long-term outcome following case management after coronary artery bypass surgery.

Patient outcome following coronary artery bypass grafting (CABG) has come under increasing governmental, social, and economic scrutiny. To insure quality patient outcome after CABG, many new policies and programs have been instituted. One of these, case management, was developed as a tool for identification and quantification of patient clinical sequences and resource utilization. This present study examines the influence of case management on length of stay and patient outcome following CABG. One hundred forty randomized, retrospectively analyzed CABG patients from 1990, prior to case management, were compared against 140 age-and case-matched randomly controlled CABG patients from 1994 after case management was in place. Patients' demographics were similar. The outcome data showed that intensive care unit (ICU) use and total length of stay were significantly decreased. Furthermore, resource utilization as monitored by chest X-ray, electrocardiography, and laboratory testing were decreased as well. Finally, mortality was decreased despite an increase in risk-adjusted acuity of the patients. There appeared to be no effect of gender or age on the benefit derived from case management. These data demonstrate that the influence of case management is beneficial for resource utilization and patient outcome following CABG and that these types of patient care policy advancements should be encouraged.

Aged

Self-care and psychosocial adjustment of patients following cardiac surgery.

This research examined the role of self-care behavior of 151 patients (aged 40 to 80) on general psychological distress at one year after coronary artery bypass graft (CABG) surgery. A tested hypothesis was that self-care practices would be associated with a lower level of distress one year after surgery. The results supported the beneficial effect of self-care on psychological adjustment, after controlling for the effects of the number of other chronic illnesses and post-CABG depression. The findings suggest that social work in health care and in-home care may help promote the psychosocial recovery process following surgery.

Adaptation, Psychological

Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery.

BACKGROUND: Atrial fibrillation occurs commonly after open-heart surgery and may delay hospital discharge. The purpose of this study was to assess the use of preoperative amiodarone as prophylaxis against atrial fibrillation after cardiac surgery. METHODS: In this double-blind, randomized study, 124 patients were given either oral amiodarone (64 patients) or placebo (60 patients) for a minimum of seven days before elective cardiac surgery. Therapy consisted of 600 mg of amiodarone per day for seven days, then 200 mg per day until the day of discharge from the hospital. The mean (+/-SD) preoperative total dose of amiodarone was 4.8+/-0.96 g over a period of 13+/-7 days. RESULTS: Postoperative atrial fibrillation occurred in 16 of the 64 patients in the amiodarone group (25 percent) and 32 of the 60 patients in the placebo group (53 percent) (P=0.003). Patients in the amiodarone group were hospitalized for significantly fewer days than were patients in the placebo group (6.5+/-2.6 vs. 7.9+/-4.3 days, P=0.04). Nonfatal postoperative complications occurred in eight amiodarone-treated patients (12 percent) and in six patients receiving placebo (10 percent, P=0.78). Fatal postoperative complications occurred in three patients who received amiodarone (5 percent) and in two who received placebo (3 percent, P= 1.00). Total hospitalization costs were significantly less for the amiodarone group than for the placebo group ($18,375+/-$13,863 vs. $26,491+/-$23,837, P=0.03). CONCLUSIONS: Preoperative oral amiodarone in patients undergoing complex cardiac surgery is well tolerated and significantly reduces the incidence of postoperative atrial fibrillation and the duration and cost of hospitalization.

Aged

The use of hibernation induction triggers for cardiac transplant preservation.

Cardiac transplant is hindered by donor shortage and preservation time. Extended extracorporeal preservation could increase the number and distribution of hearts for transplantation. Interestingly, mammalian hibernation biology closely parallels the altered cardiac cellular physiology noted with hypothermic organ storage. The present study undertook to test whether treatment with hibernation induction triggers could improve myocardial functional recovery following prolonged ischemic storage in a nonhibernating mammalian model. To study this hypothesis, isolated rabbit hearts had baseline functional and metabolic parameters recorded and then received either hypothermic storage only or standard cardioplegia, or cardioplegia containing 1 mg/kg D-Ala2-Leu5-enkaphalin (DADLE), which mimics natural hibernation, or preperfusion with DADLE, administered for 15 min at 2 mmol, 25 min prior to cardioplegic ischemia. Hearts were then subjected to 18 hr of global ischemic storage at 4 degrees C. Isovolumic developed pressure, coronary flows, and myocardial oxygen consumption were significantly improved with DADLE pretreatment vs. all groups after storage and reflow. Furthermore, DADLE hearts demonstrated better histological ultrastructure preservation following prolonged storage ischemia. This study demonstrates that hibernation protection with DADLE is beneficial for prolonged cardiac storage. The use of hibernation induction triggers is promising for organ preservation and deserve further mechanistic study.

Analysis of Variance