Biomedical subjects

S F Bolling

Publications and source records attributed to S F Bolling.

At least 55 records · Page 3Linked to original sources

PubMed1997

Phase-directed therapy and cardiac xenograft survival.

Xenotransplant rejection is facilitated not only by T cell upregulation but also by endothelial activation and B cell/antibody mechanisms, which standard immunosuppression is unable to overcome and xenorejection ensues. However, therapy directed specifically at each phase of xenorejection may improve xenograft survival. To study this we used a heterotopic cardiac xenotransplant mode (Syrian hamster to Lewis rat). Controls had no immunotherapy. Xenorecipients received cyclosporine to restrict T cellular response/development or cyclophosphamide, an antiproliferative, to reduce xenoreactive clones and antibody/complement injury, or anti-TNF antibody to alter cytokine cascades and endothelial activation/inflammation. Further xenorecipients received combinations. While single modalities alone did not enhance survival, combinations appeared to be at least additive in vivo, suggesting that therapy directed at specific phases of xenorejection may prove useful.

Animals↗

PubMed1997

Use of "natural" hibernation induction triggers for myocardial protection.

BACKGROUND: Hypothermic cardioplegia provides adequate myocellular protection, yet stunning and dysfunction remain significant problems. Interestingly, the subcellular changes of hibernation parallel the altered biology of induced cardiac ischemia, but are well tolerated by hibernating mammalian myocardium. Hibernation induction trigger (HIT) from winter-hibernating animal serum induces hibernation in active animals. Hibernation induction trigger is opiate in nature and is similar to the delta 2 opioids. METHODS: To determine whether HIT could improve myocardial recovery following global ischemia, we gave 37 isolated rabbit hearts either standard cardioplegia or cardioplegia containing summer-active woodchuck, hibernating woodchuck, or black bear HIT serum or a delta 2 opioid, D-Ala2-Leu5-enkephalin, before 2 hours of global ischemia. RESULTS: Hibernation induction trigger appeared not to have an active mechanism during ischemia, as all hearts had equal recovery. In contrast, when examining for a preischemia mechanism, 23 additional rabbits received 3 days pretreatment with summer-active woodchuck or HIT hibernating woodchuck or black bear serum, or were preperfused with D-Ala2-Leu5-enkephalin or D-pen2,5-enkephalin, a-delta 1 opioid, again before 2 hours of global ischemia. Postischemic ventricular function, coronary flows, myocardial oxygen consumption, and ultrastructural preservation were all significantly improved with HIT and D-Ala2-Leu5-enkephalin pretreatment. CONCLUSION: "Natural" HIT protection is superior to standard cardioplegia alone and may have clinical application.

Analysis of Variance↗

PubMed1997

Adjustable model of chronic left ventricular dysfunction.

BACKGROUND: As an adjunct to the development of skeletal muscle-powered left ventricular assist devices, an adjustable model of chronic left ventricular failure was developed. METHODS: Implantation of a left ventricular balloon to induce heart failure was accomplished via left thoracotomy. Upon recovery, left ventricular failure was simulated by manipulation of left ventricular balloon volume to chronically raise left atrial pressure. RESULTS: Left atrial pressure increased from a baseline of 9.3 +/- 0.7 mm Hg to 18.5 +/- 1.2 mm Hg, 20.2 +/- 1.8 mm Hg, and 26.0 +/- 1.2 mm Hg by the 2nd, 6th, and 10th postoperative week, respectively. Cardiac index declined from a baseline of 4.4 +/- 0.3 L x min(-1) x m(-2), reaching stability by the 8th postoperative week at 3.0 +/- 0.4 L x min(-1) x m(-2). Stroke volume index declined from 1.12 +/- 0.1 mL x kg(-1) x beat(-1) to 0.60 +/- 0.1 mL x kg(-1) x beat(-1) by the 10th postoperative week. Mean survival was 75 +/- 7 days. Causes of death included left ventricular failure, thromboembolism, and euthanasia. CONCLUSIONS: This method of simulating chronic left ventricular dysfunction proved to be stable and adjustable and has been useful in the development of ventricular assist systems.

Animals↗

PubMed1997

Surgical delay for acute type A dissection with malperfusion.

BACKGROUND: An acute type A aortic dissection is considered a surgical emergency. Review of the risk factors for a type A dissection showed that preoperative malperfusion was associated with a 22% (2/9) intraoperative mortality and an 89% (8/9) hospital mortality. Intraoperative deaths were secondary to pulmonary failure resulting from capillary leak; the remaining patients died of multiorgan failure resulting from reperfusion injury. METHODS: The surgical delay approach was adopted for malperfused patients, and treatment in these patients included percutaneous reperfusion, with aortic fenestration and branch stenting where appropriate. Twenty patients had a type A dissection and malperfusion shown by pulsed-wave Doppler echocardiography, transesophageal echocardiography, or spiral computed tomographic scanning. Malperfusion was documented by angiography. After reperfusion, all patients' conditions were stabilized in the intensive care unit; intravenous beta-blockers were administered to decrease the maximum rate of increase of left ventricular pressure. Once patients completely recovered from the consequences of malperfusion, surgical repair was performed. Statistical comparison of the non-delay and delay groups was performed using Fisher's exact test and Student's t test. Multiple logistic regression analysis was used to establish independent predictors for mortality. RESULTS: The mean delay to repair was 20 days (2 to 67 days). Four (31%) patients were discharged home and readmitted for operation. Three patients (15%) died preoperatively, 1 of retrograde dissection and rupture and 2 of reperfusion injury. Seventeen underwent surgical repair, with two deaths (12%); 15 (75%) were discharged, with an average follow-up of 16.8 months (p < 0.003). Delay was the only independent predictor of outcome. CONCLUSIONS: Patients with an acute type A dissection and malperfusion should undergo percutaneous reperfusion, and surgical repair should be delayed until the reperfusion injury resolves.

Adult↗

PubMed1997

CD28 blockade alters cytokine mRNA profiles in cardiac transplantation.

BACKGROUND: T-cell response to alloantigen is dependent on T-cell receptor activation and costimulation through the CD28 receptor, because T-cell receptor activation alone is insufficient for optimal immune response. The CD28 receptor on helper T cells interacts with its ligand B7 on activated B cells-macrophages as costimulus to support T-cell activity. CTLA4Ig is a recombinant inhibitor of CD28 receptor activation. In vivo studies with a rat major histocompatibility complex mismatch heterotopic cardiac transplant model demonstrate that CTLA4Ig prolongs cardiac allograft survival. This CTLA4Ig survival benefit is enhanced with prior donor-specific antigen exposure. METHODS: To investigate CTLA4Ig mechanisms, we examined the differential expression of B7 and cytokine mRNAs for interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-10 (Th1 or Th2 activation) in cardiac allografts after treatment with CTLA4Ig and donor-specific antigen exposure versus conventional immunotherapy (cyclosporine, cyclophosphamide, or antilymphocyte serum). In the above major histocompatibility complex mismatch model, hearts (on day 5 after transplantation at peak rejection) had cytokine mRNA expression determined by semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: Inhibition of B7 expression was observed in CTLA4Ig animals. Expression of IL-2 and IFN-gamma was near undetectable in CTLA4Ig and cyclophosphamide rats but was only moderately reduced by cyclosporine and antilymphocyte serum. IL-4 mRNA expression was reduced equally in all animals. Finally, IL-10 levels were unchanged by CTLA4Ig but were decreased by other therapies. CONCLUSIONS: The beneficial effect of CTLA4Ig, inhibiting expression of B7, alters Th1 cytokines IL-2 and IFN-gamma, with a resultant predominant IL-10 driven, Th2 tolerogenic response.

Abatacept↗

PubMed1997

Psychological recovery from coronary artery bypass graft surgery: the use of complementary therapies.

This study explored the use of complementary therapies that patients pursued after coronary artery bypass graft (CABG) surgery and its relation to psychological recovery, particularly postoperative distress. Information about post-CABG Surgery depression and general distress, health-care practice thereafter, perceived social support, and chronic conditions other than cardiac disease was gathered from a sample of 151 patients through two questionnaires. Additional cardiac, surgical, and demographic data were obtained from medical records. Structural equation modeling (LISREL 8) was used to test the hypothesis that patients' health-care practices improved psychological adjustment after CABG. Of the sample, 85% practiced complementary approaches, especially prayer, exercise, and lifestyle-diet modification. The number of the other chronic illnesses strongly predicted post-CABG depression and general distress. CABG patients who pursued complementary approaches, particularly exercise and prayer, had better psychological recovery.

Adaptation, Psychological↗

PubMed1997

How gender affects psychological adjustment one year after coronary artery bypass graft surgery.

This research investigated gender differences in psychological adjustment among patients (112 males, 39 females) one year after coronary artery bypass graft surgery (CABG). Information regarding post-CABG depression, non-cardiac chronic conditions, and socioeconomic variables were obtained from a survey. Additional cardiac, surgical, and demographic data were retrieved from a hospital computer database. Women were more likely than men to experience postoperative depression, attributable to their poor health. Depression one year post-CABG was predicted by non-cardiac chronic illnesses, postoperative fatigue and shortness of breath and socioeconomic status.

Adaptation, Psychological↗

PubMed1997

Reperfusion adequacy and functional recovery.

Ischemic myocardium undergoes many physiologic changes, including alterations in contractile function, histologic condition, and oxygen utilization. Reperfusion of ischemic myocardium may reverse some of these changes; however, the level of reperfusion needed for adequate functional recovery, as opposed to myocyte salvage, remains controversial. This study examines the effects of varying levels of reperfusion following ischemia on functional parameters of recovery. Isolated rabbit hearts were subjected to global ischemia at 37 degrees C for 10, 20, or 45 min. The hearts were reperfused at either mean normal baseline pressure (80 mm Hg), one half baseline (40 mm Hg), or one fourth baseline (20 mm Hg). With reperfusion, although all hearts retained the compensatory metabolic ability to upregulate oxygen extraction, reduction of reperfusion pressure resulted in depression of contractility and myocardial oxygen consumption, especially with low-pressure reperfusion. These findings suggest that all levels of reperfusion are not equal for optimal myocardial functional recovery. As minimal reperfusion may result in persistent stunning of myocardium, other means of enhancing reperfusion, such as percutaneous transluminal coronary angioplasty or coronary artery bypass grafting, should be considered.

Angioplasty, Balloon, Coronary↗

PubMed1997

Mediators of ischemia-reperfusion injury of rat lung.

In rats, we characterized the mediators of lung reperfusion injury after ischemia. Animals underwent left lung ischemia. After 90 minutes of ischemia, reperfusion for up to 4 hours was evaluated. Lung injury, as determined by vascular leakage of serum albumin, increased in ischemic-reperfused animals when compared with time-matched sham controls. Injury was biphasic, peaking at 30 minutes and 4 hours of reperfusion. The late but not the early phase of reperfusion injury is known to be neutrophil dependent. Bronchoalveolar lavage of ischemic-reperfused lungs at 30 minutes and 4 hours of reperfusion demonstrated increased presence of serum albumin, indicative of damage to the normal vascular/airway barrier. Lung mRNA for rat monocyte chemoattractant protein-1 and tumor necrosis factor-alpha peaked very early (between 0.5 and 1.0 hour) during the reperfusion process. Development of injury was associated with a decline in serum complement activity and progressive intrapulmonary sequestration of neutrophils. Administration of superoxide dismutase before reperfusion resulted in reduction of injury at 30 minutes of reperfusion. Complement depletion decreased injury at both 30 minutes and 4 hours of reperfusion. Requirements for tumor necrosis factor-alpha, interferon-gamma, and monocyte chemoattractant protein-1 for early injury were shown whereas only tumor necrosis factor-alpha was involved at 4 hours. We propose that acute (30-minute) lung injury is determined in large part by products of activated lung macrophages whereas the delayed (4-hour) injury is mediated by products of activated and recruited neutrophils.

Animals↗

PubMed1997

The economics of uncomplicated mitral valve surgery.

BACKGROUND AND AIMS OF THE STUDY: Comparisons of mitral valve (MV) replacement and reconstruction have demonstrated lower overall complication rates, better left ventricular (LV) function, and inferred overall lower cost for the latter procedure compared with the former. However, assessment of economic differences between the two procedures in routine cases, without complications, has not been reported. This study retrospectively evaluates the economic impact of uncomplicated MV repair versus replacement. METHODS: As this study seeks only to evaluate economic comparisons between routine cases of mitral repair versus replacement, those patients having concomitant procedures performed (coronary revascularization or other valve procedure) or postoperative complications (i.e. pulmonary failure, wound infections, new-onset atrial fibrillation, return for bleeding, or neurologic sequelae) were excluded from the study. Among patients who underwent uncomplicated MV procedures, 30 were selected at random and reviewed. RESULTS: Variables for MV replacement versus reconstruction included aortic cross-clamp time (112 +/- 54 versus 92 +/- 20 min; p = NS), cardiopulmonary bypass (CPB) time (189 +/- 70 versus 128 +/- 18 min; p < 0.05), total hospital stay (8.3 +/- 1.6 versus 5.6 +/- 1.6 days; p < 0.0001), and total hospital charges ($44,697 +/- 4903 versus $31,337 +/- 4484; p < 0.0001), respectively. CONCLUSIONS: These data suggest that, beyond the recognized benefits of MV reconstruction, namely preservation of LV function and avoidance of long-term anticoagulation, there is an economic advantage to MV reconstruction for patients and payors, even in uncomplicated cases. These differences may become more apparent with longer follow-up and in patients having poor function or combined procedures. This finding reinforces the idea that MV reconstruction is the option of choice for patients with mitral regurgitation.

Cardiac Surgical Procedures↗

PubMed1996

Outcome of reoperative valve surgery via right thoracotomy.

BACKGROUND: The rate of patients being referred for mitral or tricuspid valve surgery after previous cardiac surgery is expected to increase. Reoperative median sternotomy has known risks, including injury to or embolism from prior grafts, sternal dehiscence, phrenic nerve injury, excessive hemorrhage, and inadvertent cardiac injury leading to morbidity and mortality. METHODS AND RESULTS: To avoid these problems, the right thoracotomy approach for reoperative mitral or tricuspid valve surgery was used in 62 patients from January 1990 to September 1995. Average patient age was 66 +/- 12 years. Previous operations included: coronary artery bypass graft, 31; mitral valve surgery, 26 (repair, 12, replacement, 14); and aortic valve surgery, 10. Patients were cannulated via the ascending aorta or common femoral artery with bicaval venous drainage. Systemic cooling and fibrillatory arrest were used. Operations performed included mitral valve repair in 27 patients; mitral valve replacement in 18; prosthetic mitral valve replacement in 14; repair of prosthetic mitral valve leak in 2; and tricuspid valve repair in 5. There was 1 intraoperative death and 4 other hospital deaths; 30-day hospital mortality was 6.4%. Complications were uncommon; only 1 patient required reexploration for bleeding. There have been 4 late deaths, and at a mean follow-up of 27 months (range, 1 to 69 months), survivors are in New York Heart Association class I or II. CONCLUSIONS: Right thoracotomy is a safe, feasible alternative to median sternotomy for selected reoperative mitral valve patients and should be considered whenever repeat sternotomy could prove hazardous.

Adult↗

PubMed1996

Mitral valve reconstruction for active and healed endocarditis.

BACKGROUND: Mitral valve reconstruction rather than replacement for mitral insufficiency offers a number of well-accepted benefits. However, the feasibility and results of reconstruction for endocarditis remain largely unknown. METHODS AND RESULTS: We reviewed 22 consecutive patients referred to the Thoracic Surgical Service at the University of Michigan from January 1, 1991, through October 1, 1995, who underwent mitral valve reconstruction for mitral insufficiency caused by isolated mitral valve endocarditis. Mean age, preoperative ejection fraction, and New York Heart Association (NYHA) functional class were 53 +/- 15 years, 54 +/- 12%, and 3.2 +/- 0.8, respectively. Seven patients had early operation because of septic embolization, persistent infection, or refractory heart failure. Fifteen were cured of infection and were operated on for progressive symptomatic heart failure and left ventricular dilation. Preoperative transesophageal echocardiograms demonstrated severe mitral insufficiency in 20 patients. Valvular pathology noted at operation included annular (6 patients) or leaflet calcification (2), chordal rupture (13), leaflet vegetations (11), annular abscess (3), annular dilation (18), flail leaflet (12), leaflet prolapse (17), chordal shortening (1), and mitral stenosis (1). Mitral valve reconstruction included debridement of infected tissue and implantation of an annuloplasty ring (20 of 22 patients), as well as other complex techniques. Postrepair transesophageal echocardiograms demonstrated mild mitral insufficiency in 6 patients and none in 16 patients. There were no operative or in hospital deaths. Mean follow-up was 20 +/- 14 months. One late death occurred at 30 months. At follow-up, 90% of surviving patients were in NYHA functional class I or II. CONCLUSIONS: Mitral valve reconstruction for active or healed endocarditis can be performed with low operative morbidity and mortality and yields excellent functional results. Although longer-term follow-up is mandatory, these data support strong consideration of mitral valve reconstruction rather than mitral valve replacement for mitral insufficiency secondary to endocarditis.

Adult↗

PubMed1996

Improvement following correction of secondary mitral regurgitation in end-stage cardiomyopathy with mitral annuloplasty.

Twenty consecutive patients with severe mitral regurgitation secondary to end-stage dilated cardiomyopathy underwent mitral annuloplasty for refractory symptoms of heart failure. On follow-up 18 +/- 4 months after annuloplasty, 14 patients (70%) were alive, all 14 noted symptomatic improvement, and quantitative echocardiographic/Doppler demonstrated decreases in left ventricular volume and sphericity accompanied by increases in ejection fraction and forward cardiac output.

Cardiomyopathy, Dilated↗

PubMed1996

Simultaneous detection of nucleotides, nucleosides and oxidative metabolites in myocardial biopsies.

A new simple, simultaneous matrix HPLC methodology was developed to facilitate better peak separability and resolution for the determination of levels of myocardial tissue nucleotides, nucleosides and oxidative metabolites. The components of interests were ATP, AMP, ADP, IMP, hypoxanthine, xanthine, adenosine, inosine, NAD, and NADH, which are used to establish myocardial cellular energy status and effectiveness of cardioprotection. Their detection was achieved using a 4-microns spherical bead, 300 x 3.9 mm I.D. Nova-Pak C18 column in a 12% methanol mobile phase solvent selection, ion-pairing reagents 1.47 mM TBAP (tetrabutylammonium phosphate) and 73.5 mM KH2PO4, at a pH of 4.0. The extraction method was modified for rapid determination to ensure diminished acid labile NADH effects. Comparisons of peak retention (k), resolution (Rs) of solvents of varying concentrations and pH adjustment facilitated this method. This isocratic single run determination allows for simple, simultaneous rapid quantification and identification of alterations in high-energy phosphates, nucleoside degradation products and NAD/NADH levels associated with myocardial ischemia, with excellent reliability.

Adenine Nucleotides↗

PubMed1996

Dichloroacetate enhanced myocardial functional recovery post-ischemia : ATP and NADH recovery.

This study was undertaken to determine the effect of dichloroacetate (DCA) on myocardial functional and metabolic recovery following global ischemia. Isolated rabbit hearts were subjected to 120 min of mildly hypothermic (34 degrees C), cardioplegic arrest with multidose, modified St. Thomas' cardioplegia. Hearts were reperfused with either physiologic salt solution (PSS) as controls, (CON, n = 10) or PSS containing DCA (DCA, n = 6) at a concentration of 1 mM. Functional and metabolic indices were determined at baseline and at 15, 30, and 45 min of reperfusion. In four DCA and four CON hearts, myocardial biopsies were taken at baseline, end-ischemia, 15 and 45 min for nucleotide levels. Functional recovery was significantly better in hearts reperfused with DCA as demonstrated by recovery of baseline developed pressure (DCA = 69 +/- 5%, CON = 45 +/- 9%) and dP/dt (DCA = 64% +/- 10% versus CON = 48% +/- 10%). Coronary blood flow was not different between groups either at baseline or during reperfusion, but myocardial oxygen consumption (MVO2) was increased in the DCA versus CON hearts (79% +/- 20% of baseline vs 50% +/- 18%). Recovery of myocardial adenylate energy status was improved in the DCA versus CON hearts (ATP recovered to 45% +/- 20% versus 8% +/- 6% of baseline). Coronary sinus lactate concentration was decreased in DCA perfused hearts at 45 min of reperfusion. Percent of baseline NADH values was similar at 15 min of reperfusion, but at 45 min, DCA hearts showed a decrease in NADH levels, while CON hearts showed an increase (DCA = 48%; CON = 121%). The enhanced myocardial function and improved metabolic status noted with DCA may result from increased oxidative phosphorylation due to altered pyruvate dehydrogenase (PDH) activity.

Adenine Nucleotides↗

PubMed1996

The time course of CTLAIg effect on cardiac allograft rejection.

T cell response to alloantigen is dependent not only on T cell receptor activation, but also upon co-stimulation through the CD28 receptor, as T cell receptor activation alone is insufficient for an optimal immune response. The CD28 receptor on helper T cells interacts with its ligand B7 on activated B cells/macrophages as the co-stimulus to support T cell activity. The natural ligand for CD28, B7 is expressed in both constituitive and inducible forms. Expression of the inducible form, B7.1 is the most co-stimulatory and may peak at 48 hr following antigen presentation. CTLA4Ig (a soluble CD28 receptor analog) binds both B7's and inhibits CD28 activation. This experiment was undertaken to examine the optimal time course of CTLA4Ig effect at or following antigen presentation. In vivo studies used a rat MHC mismatch heterotopic cardiac allograft transplant model (Brown-Norway to Lewis). Controls received no immunotherapy. Experimental recipients received CTLA4Ig (0.05 mg i.p.) the day of transplant only or had CTLA4Ig x 7-21 days begun at Day 0, 3, or 5 following transplant. Rejection was defined as a lack of allograft contraction. Allograft survival was best when CTLA4Ig was present on Day 2. These findings demonstrate that CTLA4Ig was most effective 48 hr following antigen presentation, perhaps reflecting induction of tolerance at a time of maximal CTLA4Ig/B7.1 blockade. CTLA4Ig given later, at a time when the recognition/rejection process has already begun was not as effective indicating the lack of immunosuppressive function of CTLA4Ig itself and confirms CTLA4Ig's mechanism of co-stimulation blockade.

Abatacept↗

PubMed1996

Extended lung preservation with the use of hibernation trigger factors.

BACKGROUND: The complications of preserving lungs for transplantation are well known, with successful transplantation only being assured by preservation times of 5 to 6 hours or less. If a new method of consistent lung preservation could be identified, lung transplantation could be extended to many patients. We have previously reported lung preservation times averaging 14.8 hours using a multiorgan autoperfusion block infused with physiologic saline solution as a model. When plasma from deeply hibernating woodchucks (Marmota monax) or the delta opioid DADLE was infused into the multi-organ block, lung preservation times increased threefold to 45 hours. METHODS: In this study, we examined the effect of infusing plasma containing the hibernation induction trigger molecule on lung preservation for transplantation using a multiorgan autoperfusion block. RESULTS: This study demonstrated that successful orthotopic transplantation of single canine lungs is possible after 24 to 33 hours of preservation when the lung has been maintained with plasma containing the hibernation induction trigger molecule. CONCLUSIONS: Theoretically, hibernation induction trigger could be administered to donors before lung harvest in an effort to extend lung preservation times.

Animals↗

PubMed1996

Mitral valve reconstruction in sickle cell disease.

As survival improves in patients with sickle cell anemia, the prospects of performing cardiac surgical procedures on older patients with this genetic defect increase. We describe the successful management of a 52-year-old patient with sickle cell disease (homozygous for hemoglobin S) and a history of multiple sickle crisis undergoing cardiopulmonary bypass for mitral valve repair. Preoperative partial exchange transfusion followed by total exchange transfusion at the time of operation was performed to reduce the level of hemoglobin S to 5.4% during bypass. Other management strategies included high-flow normothermic bypass with aortic crossclamping, topical hypothermia, and cold crystalloid cardioplegia.

Anemia, Sickle Cell↗