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Biomedical subjects

S F Bolling

Publications and source records attributed to S F Bolling.

At least 145 records · Page 8Linked to original sources

Protection of the neonatal heart following normothermic ischemia: a comparison of oxygenated saline and oxygenated versus nonoxygenated cardioplegia.

Optimal methods of myocardial preservation in the neonate remain unknown. Hypothermia and cardioplegia have been shown to protect neonatal hearts, but few studies have examined the effects of cardioplegia when administered at normothermia. Accordingly, the role of 37 degrees C St. Thomas' cardioplegic solution in protecting the neonatal heart during 1 hour of ischemia in an isolated working rabbit heart model was examined. Both oxygenated and nonoxygenated cardioplegic solutions (CSs) were evaluated and compared with an oxygenated physiological saline solution (PSS). Following ischemia, control hearts were characterized by severely impaired left ventricular function, whereas all three treatment groups recovered well, indicating that the treatments provided substantial protection. Aortic flow recovered to 62, 63, and 57% of preischemic values for the oxygenated CS, nonoxygenated CS, and oxygenated PSS groups, respectively. Similarly, rate of change of pressure recovered to 76, 80, and 76% of preischemic values for oxygenated CS, nonoxygenated CS, and oxygenated PSS groups. All values were significantly greater than those for the control group. Recovery of developed pressure was significantly improved in all three groups. End-diastolic pressure rose markedly following ischemia in control hearts, was not increased after ischemia in hearts receiving oxygenated and nonoxygenated CS, but was increased in the oxygenated PSS group. These data indicate that crystalloid cardioplegia and oxygenated PSS provide substantial protection in neonatal rabbit hearts, even when delivered at 37 degrees C. No additional benefit was seen when the cardioplegic solution was oxygenated. Therefore, either method of balancing the oxygen supply/demand ratio appears to be beneficial: supplying oxygen intermittently during ischemia (oxygenated PSS group) or decreasing oxygen demand during the ischemic period (cardioplegia groups).

Animals↗

The effect of hypothermic ischemia on recovery of left ventricular function and preload reserve in the neonatal heart.

Neonatal and adult myocardium respond differently to ischemia. In addition, the neonatal heart possesses a limited preload reserve. The effect of uninterrupted hypothermic ischemia on recovery of left ventricular function and preload reserve was studied in two groups of isolated rabbit hearts: group 1 (neonates, n = 8), 7 to 10 days old; group 2 (adults, n = 15), 6 to 12 months old. Peak left ventricular systolic pressure, the first derivative of left ventricular systolic pressure, and heart rate were measured at left ventricular pressures of 0, 5, 10, and 15 mm Hg before and after 120 minutes of global ischemia at 27 degrees C. Before ischemia, left ventricular systolic pressure increased significantly at each increment of left ventricular end-diastolic pressure for both groups of hearts. After hypothermic ischemia, recovery of left ventricular systolic pressure was significantly reduced at each level of left ventricular end-diastolic pressure among neonatal hearts (range 75% to 79% of control values). The postischemic recovery of left ventricular systolic pressure in the adult hearts was markedly reduced from baseline values (range 43% to 53% of control values) and was significantly worse than that of neonatal hearts at each level of left ventricular end-diastolic pressure (p less than 0.001). Both groups were able to respond to increasing preload after ischemia. The slope of the curve describing the relationship between left ventricular end-diastolic pressure and percent recovery of left ventricular systolic pressure was not different from zero for neonatal hearts but was significantly greater than zero among the adults (0.22 +/- 0.21 versus 0.73 +/- 0.07, p = 0.0056). After ischemia, the first derivative of left ventricular systolic pressure fell significantly from control values among neonatal hearts (71% of control values). The reduction was considerably greater, however, among the adult hearts (54% of control values). These data indicate that the neonatal heart recovers systolic function better than the adult heart after global ischemia with moderate hypothermia.

Aging↗

Progression and resolution of myocardial reflow injury.

The development of and recovery from a severe yet nonlethal myocardial injury following hyperkalemic cardioplegia and prolonged hypothermic global ischemia was examined over 14 days in a rat model of heterotopic intraabdominal cardiac isograft transplantation. Mitochondrial enzymatic markers of myocardial ischemic injury and light microscopic signs of damage were examined. Eighteen hearts were arrested in situ using hyperkalemic cardioplegia and subjected to a mean of 38 min of ischemia at 20 degrees C as transplantation was achieved. No changes in mitochondrial creatine kinase (CKm) activity, mitochondrial malate dehydrogenase (MDHm) activity, their ratio, or morphologic evidence of injury were found during 8 days of reperfusion. In a second group of 66 hearts, the duration of hypothermic cardioplegic ischemia was extended by 120 min before transplantation. Neither unreperfused hearts nor hearts reperfused for only 1 hr demonstrated significant depression of enzyme activities or microscopic evidence of injury. However, after 1 day of reperfusion, CKm and MDHm activities were depressed to 36 and 44% of control levels (P less than 0.05). These activities had returned to control levels by 2 days of reperfusion and remained stable for 12 days thereafter. Light microscopic analysis revealed cellular injury to be maximal at 1 to 2 days of reperfusion with gradual improvement noted over the following 12 days. These observations suggest the existence of a mitochondrial injury following prolonged cardioplegic arrest and hypothermic global ischemia that is maximal after 24 hr of reperfusion but shows evidence of improvement thereafter. These findings justify aggressive support of the poorly functioning heart for the first few days after prolonged global ischemia.

Animals↗

Identification and control of noncoronary collateral blood flow.

To identify the source of noncoronary collateral myocardial blood flow and to establish methods to control it during induced ischemia, 29 dogs were placed on cardiopulmonary bypass. The right and left ventricles were vented, vent flows were measured volumetrically, and intracavitary left ventricular (LV) pressures were monitored. After induction of ischemia by aortic cross-clamping and infusion of cardioplegic solution, six different microspheres 7 to 10 microns in diameter were injected into the aorta at six different times to measure myocardial blood flow during the following interventions:vent drainage of the right or left ventricle or both, proximal ligation of both coronary arteries, severance of the proximal pulmonary artery or the ascending aorta or both, and ligation of the bronchial arteries. Without effective LV venting, LV intracavitary pressure rose to 7.0 +/- 0.1 mm Hg (mean +/- standard error of the mean) and myocardial blood flow in the anterior left ventricle was 2.3 +/- 1.3 ml/100 gm/min. When the LV vent was opened, vent flow was 35.9 +/- 3.5 ml/min and myocardial blood flow fell to 0.3 +/- 0.2 ml/100 gm/min. Right ventricular (RV) vent flow was absent except when the LV vent was occluded, and this RV vent flow was abolished by ligating the coronary arteries. With bronchial artery ligation, LV vent flow ceased and myocardial blood flow was virtually absent. These studies demonstrate that myocardial blood flow does occur during induced ischemia, but that the source of this blood flow is primarily through systemic-pulmonary channels. True noncoronary collateral myocardial blood flow was virtually nonexistent.

Animals↗

The mechanism of mannitol in reducing ischemic injury: hyperosmolarity or hydroxyl scavenger?

The effectiveness of postischemic reperfusion with mannitol has been well documented in previous studies. Mannitol, a hyperosmolar agent, is also an effective scavenger of the cytotoxic hydroxyl radical. If mannitol acts solely as a hyperosmolar agent, hyperosmolar reperfusion with its isomer, glucose, should be equally effective. To elucidate the beneficial effect of mannitol, 24 isolated rabbit heart preparations were subjected to 60 min of hypothermic (27 degrees C) cardioplegic arrest and normothermic reperfusion. There were three study groups with eight hearts in each. Group I hearts were reperfused with an unmodified isosmolar solution. Group II hearts were reperfused with a hyperosmolar (350 mOsm/liter) solution containing glucose, and group III hearts had hyperosmolar (350 mOsm/liter) reperfusion with mannitol. Left ventricular function (developed pressure and maximum positive dP/dt) was measured isovolumically before and after ischemia. Coronary flow was measured volumetrically during reperfusion, and myocardial edema formation was determined after 45 min of reperfusion. Reperfusion with mannitol resulted in significant improvement in recovery of developed pressure (77.3 +/- 2.8% of control vs 65.5 +/- 2.9% in group I and 62.6 +/- 2.2% in group II; p less than .05). Mannitol-treated hearts also had significantly greater coronary flow throughout the reperfusion period and significantly less marked myocardial edema formation compared with hearts treated with isosmolar and hyperosmolar glucose. These data confirm the particular usefulness of mannitol in improving postischemic ventricular function, maintaining coronary blood flow during early reflow, and reducing myocardial edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Propranolol-induced postoperative hypertension following coronary artery bypass grafting.

Fifteen patients receiving propranolol preoperatively and undergoing coronary artery bypass grafting had serum propranolol levels determined preoperatively and at several times early postoperatively. In addition, the patients' hemodynamic parameters and postoperative sodium nitroprusside dose requirements were monitored. All patients had significant multivessel disease and normal left ventricular function. Preoperative serum propranolol levels ranged from 16 to 243 ng/ml, with a mean level of 92 +/- 17 ng/ml; propranolol measured at the end of bypass ranged from 0 to 92 ng/ml, with a mean level of 23 +/- 7 ng/ml. Fourteen patients (93%) had hypertension postoperatively and required intravenous sodium nitroprusside to maintain mean blood pressure at or below 90 mm Hg. According to linear regression analysis, the severity of the postoperative hypertension or, specifically, the nitroprusside dose requirements, correlated significantly with the patients' serum propranolol levels postoperatively (correlation coefficient, R = 0.76, with p less than 0.001). The one normotensive patient had no detectable serum propranolol at any time postoperatively. No correlation was noted between the patient's preoperative serum propranolol levels and the need for nitroprusside therapy postoperatively. These results demonstrate that there is a significant relationship between residual propranolol and the development of hypertension postoperatively.

Adult↗

Improved myocardial preservation during global ischemia by continuous retrograde coronary sinus perfusion.

To investigate whether retrograde continuous low-pressure perfusion of the coronary sinus could deliver cardioplegic solutions with oxygen and substrate beyond stenoses and result in improved myocardial preservation, we subjected 41 canine hearts to 90 minutes of ischemia with an occlusion on the circumflex coronary artery. There were four groups: Group I, antegrade (aortic root) crystalloid cardioplegia every 30 minutes during ischemia; Group II, antegrade plus topical cooling; Group III, continuous retrograde perfusion; Group IV, same as Group III, with an oxygenated perfluorocarbon. All solutions had a PO2 of 400 to 500 mm Hg. Intramyocardial oxygen and carbon dioxide tensions (PO2 and PCO2) and mean myocardial temperatures were monitored during ischemia, and left ventricular (LV) function was assessed before ischemia and after reperfusion. After global ischemia, the circumflex occlusion was released and the hearts reperfused. Following 60 minutes of reperfusion, isovolumic developed pressure returned to 36% +/- 4% and 41% +/- 5% of preischemic levels, respectively, in Groups I and II. By contrast, Groups III and IV (retrograde perfusion) had a significantly greater percent of recovery (78% +/- 5% and 73% +/- 5%). Circumflex area intramyocardial PO2 fell 20 and 25 mm Hg below preischemic levels in Groups I and II during ischemia, whereas in Group III, intramyocardial PO2 in the circumflex region remained near preischemic levels, and in Group IV, it rose 19 mm Hg. Mean myocardial temperature during ischemia in the circumflex area was significantly higher in Group I than in Groups II, III, and IV. Peak intramyocardial PCO2 in the circumflex region was significantly less in the retrogradely perfused hearts. Retrograde coronary sinus perfusion resulted in significant improvement in recovery of LV function, uniform myocardial cooling, normal intramyocardial PO2, and less intramyocardial PCO2 accumulation, despite the presence of a total circumflex coronary artery occlusion.

Animals↗

Enhanced myocardial protection with verapamil prior to postischemic reflow.

Reperfusion of the heart after induced myocardial ischemia may be associated with severe myocardial damage, characterized by massive calcium influx and accumulation in the heart cells. The present study was undertaken to investigate whether verapamil, a slow channel calcium blocker, administered prior to reperfusion, might reduce this reflow injury without causing depression of heart function. Thirty-two isolated, perfused rabbit hearts were subjected either to 45 minutes of normothermic or 150 minutes of hypothermic global ischemia. Half of the heart in each group received verapaMil immediately prior to reperfusion, while the remaining hearts received no verapamil. Following ischemia and 60 minutes of reperfusion, left ventricular (LV) contractivity was superior in both groups of verapamil-treated hearts, compared to control hearts (LV developed pressure [DP] in normothermic hearts 63 +/- 6% of preischemic DP for verapamil-treated hearts versus 46 +/- 6% of preischemic DP for control hearts; in the hypothermic group, 65 +/- 8% of preischemic DP for verapamil-treated hearts versus 33 +/- 10% DP for control hearts). Postischemic LV compliance also was significantly improved in the verapamil-treated hearts through the period of reperfusion, compared to control hearts. No differences were noted in coronary flow, myocardial water content, or the onset of electromechanical activity between the verapamil and control hearts, but there was significantly improved ultrastructural preservation in both verapamil groups. These data demonstrate that verapamil, when administered just prior to reperfusion, results in improved recovery of myocardial function and excellent cellular preservation, presumably for reducing calcium influx into myocardial cells.

Animals↗

Mini-reoperative mitral valve surgery.

BACKGROUND: Reoperative surgery involving the atrioventricular valves places the patient at risk for cardiac or bypass graft injury upon reoperative sternotomy. Standard right thoracotomy can avoid these problems but is associated with a large incision and possibly more pulmonary complications. METHODS AND RESULTS: An alternative, minimally invasive approach for reoperative atrioventricular valve surgery was studied in 22 patients. Patient age was 66 +/- 10 years. Postoperative mitral regurgitation was 3.4 +/- 0.3 and New York Heart Association (NYHA) Class was III/IV, despite a mean ejection fraction of 44 +/- 14%. These patients had 1-4 prior procedures a mean of 5 years previously. An anterior 5th interspace incision of 5- to 10-cm was performed. A 1-cm segment of 5th rib was removed to facilitate exposure. Cardiopulmonary bypass was performed via ascending aorta or femoral artery cannula and bicaval venous cannulae. Systemic cooling (25 degrees) and fibrillatory arrest was used. Operations performed included mitral valve repair (12), mitral valve replacement (5), prosthetic mitral valve rereplacement (4), repair of perivalvular leak (3), tricuspid valve repair (5), and atrial septal defect closures (7). Mean bypass time was 109 +/- 21 minutes with a mean fibrillatory time of 62 +/- 12 minutes. There was no intraoperative or 30-day mortality. Patients were weaned from ventilation at a mean of 5 hours postoperatively and received 1.3 +/- 1 unit of blood. There were no wound complications or re-explorations for bleeding. At a mean follow-up of 15 +/- 8 months, survivors are NYHA Class I-II. When interviewed, all patients felt their recovery was more rapid and less painful than their original sternotomy. CONCLUSION: This minimally invasive approach to reoperative atrioventricular valve surgery is safe and technically feasible. It has become our preferred approach to the atrioventricular valves in patients with a previous sternotomy.

Aged↗

Designing clinical trials on energy healing: ancient art encounters medical science.

Demand for energy healing is growing rapidly in the United States. Until recently, however, few clinical trials have been conducted to investigate its clinical efficacy, risks, and cost-effectiveness. This article discusses principles underlying the research design of clinical trials on energy healing, based on the experience of an interdisciplinary team conducting a large-sample clinical study on qigong funded by the National Institutes of Health. The first part overviews the background and contemporary practice of qigong therapy. The second addresses some difficulties and unique issues to be considered in designing a clinical trial on energy healing. These issues include research emphasis on outcome versus mechanism, randomization, control, expectations/placebo effects, staff and practitioner bias/conflict of interest, patients' belief, selection bias, intent-to-treat analysis, ethics, informed consent, sample size, and outcome report. The ultimate goal is to promote more scholarly and clinical discussion on the evaluation of energy healing.

Breathing Exercises↗

Antibodies against tumor necrosis factor prolong cardiac allograft survival in the rat.

Tumor necrosis factor (TNF)-alpha has significant biologic actions in many circumstances, such as infectious diseases, ischemia/reperfusion injury, and delayed-type hypersensitivity reactions. Based on the hypothesis that manipulation of TNF can play an important role in treatment of heart transplant rejection, the objective of this study was to determine whether anti-TNF antibodies could prolong cardiac allograft survival. Hearts from brown rats were transplanted to the necks of recipient Lewis rats. Graft survival was determined by direct palpation of the heart; complete graft rejection was defined by cessation of contraction. In untreated rats, the hearts were rejected 6.8 +/- 0.6 days (n = 10; mean +/- SEM) after transplantation. The mononuclear cell infiltrate in the transplanted hearts stained intensely for TNF by immunohistochemistry, indicating that TNF was present within the inflammatory cells associated with the rejection process. In rats receiving a single injection of anti-TNF antibody at the time of transplantation (n = 6), however, graft survival was nearly doubled (12.7 +/- 1.4 days; p less than 0.001 vs controls). Prolonged cardiac graft survival was also evident if the anti-TNF treatment was delayed until 1 day (n = 5; rejection at 16.2 +/- 2.4 days; p less than 0.001 vs controls) or even 3 days after transplantation (n = 5; rejection at 11.4 +/- 2.3 days; p less than 0.005 vs controls). Treatment at 5 days after transplantation, however, was not effective (n = 3; rejection at 7.7 +/- 0.6 days; p, not significant vs controls). The data indicate that a single bolus of anti-TNF antibodies can delay heart transplant rejection, even when administered up to 3 days after implantation, supporting the potential utility of anti-TNF therapy for treatment of heart transplant rejection.

Animals↗

Automatic internal cardioverter defibrillator: a bridge to heart transplantation.

The automatic internal cardioverter defibrillator (AICD) is effective in preventing death in patients with malignant ventricular arrhythmias (VT/VF) refractory to medical therapy. Because of the long waiting period for heart transplantation and the high likelihood of sudden arrhythmic death in this population, this study was undertaken to assess the value of the AICD in patients awaiting heart transplantation who have refractory VT/VF. Fourteen patients awaiting heart transplantation who had a history of VT/VF underwent AICD implantation (10 extrapericardial and four intrapericardial) via median sternotomy. All patients survived the AICD implantation and have either had heart transplantation or await transplantation at present (1 to 24 months after AICD implantation). Twelve of these patients have received a mean of 10 AICD shocks (range, 0 to 32). One patient received 19 shocks in the 24-hour period before transplantation. Two patients have died of progressive heart failure. Five patients have gone on to successful transplantation, and seven patients await heart transplantation with a functioning AICD in place. In conclusion, the AICD represents a new "bridge" to heart transplantation that is well tolerated by these high-risk patients, avoids drug side effects, and is efficacious in aborting sudden death, thereby allowing them to undergo successful heart transplantation.

Actuarial Analysis↗

Local cyclosporine immunotherapy of heart transplants in rats enhances survival.

High-dose systemic cyclosporine (CyA) administration frequently results in severe side effects. To evaluate a means of limiting the adverse effects of CyA, we implanted CyA-collagen matrices (0.2 or 1 mg/kg/day released) around the cardiac homografts at the time of rat heterotopic (neck) heart transplantation. Control animals received empty collagen (nondrug) matrix implants. A fourth group received CyA matrix (1 mg/kg/day released), implanted in a distal subdermal leg pouch at the time of heart transplantation. Rejection was determined by the absence of contraction in the transplanted heart. No animal received any other immunosuppression. Parallel groups of animals had whole blood, heart, and kidney CyA levels measured on the sixth posttransplant day. Local immunosuppression with high-dose CyA in a controlled-release matrix resulted in a significant survival advantage (mean survival time, 17.1 days; control, 6.9 days; p less than 0.001). The lower dose of CyA also demonstrated significant survival benefits (10.1 days), with clinically negligible blood CyA levels and very low kidney CyA levels. Both doses of epicardial local release CyA were well absorbed locally, resulting in very high CyA levels in cardiac tissue. Local immunotherapy of transplanted hearts with CyA was shown to be an effective means of preventing rejection. If this technology can be developed, this approach may prove advantageous clinically, both in extending transplantation and in minimizing systemic side effects of immunosuppression.

Animals↗

Clinical experience with the Nimbus pump.

The Nimbus pump is an indwelling, electromagnetic powered left ventricular (LV) assist device inserted transfemorally. The inflow cannula (7 mm) is positioned across the aortic valve and the pump in the descending aorta. Indications for insertion include cardiogenic shock despite maximal medical support and PCWP greater than 18 mmHg, MAP less than 90 mmHg, and Cl less than 2 L/min/m2. Twelve patients underwent the attempt at surgical insertion of the Nimbus pump. Diagnoses included eight acute myocardial infarctions (AMI), two ischemic cardiomyopathy, one postpartum cardiomyopathy, and one transplanted heart rejection. Eight (67%) of twelve patients had successful insertion. One patient had peripheral vascular disease preventing passage, and three had femoral vessels too small for insertion (less than 7.5 Hagar dilator). Five patients with the diagnosis of AMI had successful insertion and three (60%) underwent sufficient LV recovery for removal of the device; the other two patients died of stroke and ventricular arrhythmias, respectively. Three patients with the diagnosis of cardiomyopathy had progression of the disease process, and their needs exceeded the capabilities of the pump and they died of multiorgan failure. The Nimbus pump is an attractive LV assist device because of its pumping capacity (3.5 L/min) and minor surgical procedure for insertion. However, its application is limited because of access route and size. The device appears to work well for patients in cardiogenic shock after AMI (60% recovery) but does not appear indicated for patients with cadiomyopathy.

Adult↗

Experimental heterotopic heart transplantation without ischemia or reperfusion.

Current experimental models of heart transplantation include a period of ischemia after donor harvest, resulting in rhythm disturbances, myocardial distention, and reperfusion injury on implantation. A model of cervical heterotopic heart transplantation that avoids ischemia by using retrograde perfusion was developed. More than 100 consecutive successful transplantations have been performed both as control protocols and as a part of experimental protocols. The advantages of this technique include: avoidance of ischemia and reperfusion injury, prevention of myocardial damage caused by overdistention, and potential evaluation of pretreatment regimens for transplanted hearts.

Animals↗

Methylprednisolone pulsing of heart transplant patients in the home.

Methylprednisolone pulsing is the first form of treatment used to reverse acute moderate rejection in heart transplant patients at the University of Michigan, Ann Arbor. Before May 1986, patients who needed administration of medications to be pulsed were admitted to the hospital. With our increasing number of transplant patients, lack of hospital beds, and efforts toward cost containment, a new system was established. From June 1986 to April 1988, 53 heart transplantations were performed in 40 adults and 13 children. Home care agency nurses received in-service training by the heart transplant clinical specialist. Insurance companies were contacted directly to obtain financial approval when it was not considered a covered benefit. Of 47 episodes of rejection, 45 were successfully treated in the home with resolution, whereas hospital admission was required in two cases of rejection episodes for successful resolution. There were marked financial savings, increased patient satisfaction, no patient infections, and minimal side effects, which included hypertension in five patients, headaches in two patients, and difficulty gaining venous access in two patients. Most problems were easily handled by telephone communication. Therefore, after a 22-month experience with administration of methylprednisolone pulses in the home, we believe that this is a satisfactory method of treating patients. It is cost-effective, has minimal side effects, and leads to increased patient satisfaction.

Costs and Cost Analysis↗