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Biomedical subjects

J N Cunningham

Publications and source records attributed to J N Cunningham.

At least 91 records · Page 5Linked to original sources
PubMed1986

Targeting of tumor-associated antigens (TAA) in experimental immunotherapy.

We have previously shown the superiority of tumor-associated antigens (TAA) to function as effective immunogens when administered with bilayer membrane vesicles called liposomes. The ability of liposomes to target TAA to host antigen-presenting cells is analyzed here. 1-Butanol extracted TAA from two syngeneic rat colon cancer tumors (WB 2054 and W 1756) was radioiodinated (131I-TAA). Free 131I and 131I-TAA (2.8 X 10(7) cpm and 75 micrograms TAA per rat) were used as tracers, with or without incorporation into liposomes (composition: sphingomyelin, cholesterol, dicetyl phosphate at 70:24:6 molar ratio). Six groups of male rats (BN X WF for WB2054 and Wistar/Furth for W1756, n = 18 each group) were injected iv with either free tracers or the tracers incorporated into liposomes. Whole blood clearance curve was biphasic (half-life alpha = 5 min; half life beta = 12 hr), suggesting a two-compartmental model of distribution. Seven animals from each group were sacrificed at set times (15 min to 48 hr), organs harvested and cpm/g of tissue estimated. Liposome 131I and liposome 131I-TAA were targeted to and retained preferentially in liver and spleen. Four animals from each group were imaged serially using a gamma camera. Matched pair analysis of regions showed persistently higher activity in liver-spleen area when liposomes were used (P less than 0.001). The uptake of radiolabeled antigens by plastic adherent mononuclear cells in liver and spleen was significantly higher when presented with liposomes (macrophage uptake index: liver = 1.65 vs 0.55; spleen = 5.85 vs 1.15; with and without liposomes, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cryopreserved homologous saphenous vein: early and late patency in coronary artery bypass surgical procedures.

Autologous saphenous vein has proved to be a satisfactory conduit for use in coronary artery bypass grafting. Unfortunately, it is not always available, and substitute material must sometimes be used. When satisfactory autologous veins were not available and the internal mammary arteries were unsuitable, cryopreserved homologous saphenous veins were used in 28 patients. A total of 76 grafts were constructed. Cryopreserved homologous veins were used for 61 grafts, autologous saphenous veins for 11 grafts, and the internal mammary artery for 2 grafts. Coronary angiography was performed 8 to 12 days postoperatively in 16 patients. Of the 31 homografts studied, 8 were occluded (26%), 3 were stenotic (9%), and 20 were normal (65%). The one internal mammary artery and six autologous veins studied were all patent. Six patients underwent late catheterization 6 to 12 months postoperatively. Thirteen homografts were studied at late catheterization: 11 were occluded, 1 was severely stenotic, and 1 was mildly stenotic. At late catheterization, the one internal mammary artery studied was patent, and the one autologous saphenous vein was 95% occluded. Results of both early and late catheterization performed on 18 patients demonstrated that of the 35 homografts studied, 17 (49%) were occluded, 3 (9%) had greater than 70% stenosis, 1 (3%) had mild disease, and 14 (40%) were free of disease. One year follow-up data obtained on 26 patients revealed that 4 patients (15%) died of cardiac causes, 2 patients (8%) died of noncardiac causes, 11 patients (42%) have recurrent angina, and 9 (35%) are asymptomatic. It is concluded that use of cryopreserved homologous saphenous veins for coronary artery bypass grafting should be avoided if at all possible.

Adult↗
PubMed1986

Prevention of reperfusion injury of the ischemic spinal cord: use of recombinant superoxide dismutase.

We investigated the effect of recombinant superoxide dismutase, an oxygen free radical scavenger, on the prevention of reperfusion injury of the ischemic spinal cord. Somatosensory evoked potentials (SEPs) were obtained in 23 dogs. Spinal cord ischemia was produced by cross-clamping the descending thoracic aorta just distal to the origin of the left subclavian artery through a left thoracotomy. Mean proximal aortic blood pressure was maintained between 90 and 100 mm Hg by partial exsanguination. Serial SEPs were obtained at 60-second intervals until the SEP disappeared. Aortic cross-clamping was continued for 10 additional minutes after the disappearance of the SEP. In Group 1 (N = 8), no medication was given when the aortic cross-clamp was removed. In Group 2 (N = 8), a bolus of 25,000 units of superoxide dismutase was injected into the proximal aorta prior to removal of the aortic cross-clamp, and was followed by 5,000 units per minute for 10 minutes after release of the cross-clamp. In Group 3 (N = 7), 50,000 units of superoxide dismutase was administered as a bolus prior to removal of the aortic cross-clamp, followed by an additional 10,000 units per minute for 10 minutes as in Group 2. The postoperative neurological status was assessed by Tarlov's criteria. There was no significant difference in aortic cross-clamp time among the three groups. Paraplegia developed in 4 animals in Group 1; the remaining 4 dogs had paraparesis. In Group 2, paraparesis developed in 2 of 8 dogs; the other 6 had no neurological injury. All the animals in Group 3 had complete recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Postoperative ST-segment elevation in coronary artery bypass surgery.

Using Holter monitors, 50 patients were monitored for vasospasm following coronary artery bypass surgery. Transient 2 mm ST-segment elevation was considered to be diagnostic or coronary vasospasm. Four patients (8 percent) had evidence of coronary vasospasm. Over 30 variables, including preoperative demographic information and medication, intraoperative technique, and postoperative medication, were subjected to multiple stepwise regression analysis. This analysis failed to show any association between preoperative prophylaxis with either nifedipine or nitrates (or other variables) and the postoperative development of coronary vasospasm. We conclude that the incidence of coronary vasospasm is more common than previously thought, and that a nifedipine or nitrate withdrawal, in this study, was not associated with an increased incidence of postoperative coronary vasospasm.

Aged↗
PubMed1986

Acute spinal cord ischemia: prevention of paraplegia with verapamil.

Although irreversible damage to the central nervous system has been considered inevitable after 6 min of circulatory deprivation, there has been evidence for almost 20 years that this may be the consequence of postischemic events. Recent investigations have implicated calcium-mediated phenomena as responsible for damage to neuronal cells in the reperfusion period. We studied the effect of verapamil on the neurologic sequelae of spinal cord ischemia using somatosensory evoked potential monitoring in a canine preparation of spinal cord ischemia. Ten mongrel dogs weighing between 20 and 30 kg each were divided into two groups. The experimental group was pretreated with 0.4 mg/kg verapamil and the control group received no treatment. The thoracic aorta was then occluded. Flow was restored 17 min after there was complete loss of somatosensory evoked potentials. Experimental dogs received additional doses of verapamil upon reperfusion and at 1, 2, 3, 4, 5, 6, and 10 hr after reperfusion. Four of five verapamil-treated dogs were able to walk postoperatively, whereas all of the control dogs suffered dense paraplegias (p = .02). We conclude that verapamil can ameliorate the sequelae of spinal cord ischemia and that this preparation is suitable for the study of the mechanisms of ischemic neuronal damage in an area outside the brain.

Animals↗
PubMed1986

Strategy for treatment of acute evolving myocardial infarction with pulsatile left heart assist device. Can this modality increase survival and enhance myocardial salvage?

This article describes the technique of left heart bypass in the treatment of both experimental and clinical acute myocardial infarction. A new technique of closed-chest percutaneous left heart bypass that can be used in patients with acute evolving myocardial infarction and cardiogenic shock is also described.

Acute Disease↗
PubMed1986

Surgical results for mitral regurgitation from coronary artery disease.

Results of coronary artery bypass grafting with and without mitral valve replacement were analyzed retrospectively in 101 patients with preoperative ischemic mitral regurgitation to determine the effects of severity and surgical treatment of mitral regurgitation on survival. Between 1980 and 1984, a total of 1,475 patients (mean age 59, 77% male) underwent coronary bypass. These patients were divided into three groups: (1) patients without ischemic mitral regurgitation who underwent isolated coronary bypass (1,374; 93%), (2) patients with ischemic mitral regurgitation who underwent isolated coronary bypass without valve replacement (85; 6%), and (3) patients with ischemic mitral regurgitation who underwent combined mitral valve replacement and coronary bypass (16; 1%). Preoperatively, patients with ischemic mitral regurgitation compared to those without regurgitation were significantly older (+6 years, p less than 0.001), had more severe coronary artery disease (p less than 0.001), a higher incidence of congestive heart failure (24% versus 5%, p less than 0.001) and recent myocardial infarction (16% versus 8%, p less than 0.01), and a lower mean ejection fraction (45% versus 61%, p less than 0.001). Operative mortality was significantly increased in patients with ischemic mitral regurgitation who underwent coronary bypass alone (p less than 0.01) and in those who underwent coronary bypass and mitral valve replacement (p less than 0.01)--11% and 19%, respectively--than in the coronary bypass patients without ischemic mitral regurgitation (3.7%). The severity of mitral regurgitation (0 to 4+) proved to be the most significant predictor of operative mortality. The actuarial survival rate at 5 years for the coronary bypass patients without ischemic mitral regurgitation was 85% compared to 91% (p less than 0.05) for the coronary bypass patients without ischemic mitral regurgitation. These results indicate that patients with ischemic mitral regurgitation have a higher prevalence of cardiac risk factors and are at an increased risk of operative mortality. Although the severity of the ischemic mitral regurgitation was strongly predictive of early survival, it proved to have an unexpectedly modest effect on long-term survival after surgical treatment.

Actuarial Analysis↗
PubMed1986

Efficacy of right ventricular unloading during right coronary artery occlusion in an experimental model.

This investigation examined the efficacy of right atrial-pulmonary artery bypass (RA-PA) during acute ischemia of the right ventricle. The right coronary artery (RCA) was ligated in 25 open chest, open pericardium sheep. Control animals (n = 15) were resuscitated with only intravenous fluids. In the experimental animals (n = 10) RA-PA bypass was initiated 5 minutes after right coronary occlusion. Sixty percent (9/15) of the control animals died within 90 minutes of RCA occlusion from refractory ventricular arrhythmia or right ventricular failure. Four of 10 RA-PA animals died within 2 hours of RCA occlusion from severe pulmonary hemorrhage and arterial oxygen desaturation when high flow rates (2.5 to 3.5 L/min) were initially instituted. In these animals, lung histologic findings demonstrated extensive hemorrhage into the alveolar spaces. After 6 hours of RCA occlusion in the six surviving control animals, there were significant increases in central venous pressure and right ventricular end-diastolic cord length (relative ventricular volume change measured by ultrasonic crystal analysis), and a significant decrease in the cardiac output. In contrast, during RCA occlusion in the six surviving animals on RA-PA bypass, cardiac output was well maintained, and there was a significant decrease in central venous pressure and end-diastolic length. The percent of change from baseline in end-diastolic length correlated inversely with the percent of change from baseline in cardiac output (r = -0.81, p less than 0.01). By crystal violet and triphenyltetrazolium chloride dye techniques, the mean percentage area of necrosis to area of risk was significantly less for the RA-PA group compared with the control group (5.6% versus 67.1%, p less than 0.0001). In this experimental model, RA-PA bypass effectively unloaded the acutely ischemic right ventricle, maintained systemic cardiac output, and significantly reduced right ventricular infarction size. Further investigations with this ventricular support modality are needed to determine its effects on pulmonary pathophysiology.

Animals↗
PubMed1986

Time course of effective interventional left heart assist for limitation of evolving myocardial infarction.

Previous work has shown that if pulsatile left atrial-femoral artery bypass is instituted after occlusion of the left anterior descending coronary artery for from 15 minutes to 2 hours, it can significantly limit the size of the infarct resulting 4 hours later. This study investigated whether pulsatile left atrial-femoral artery bypass begun after more clinically pertinent periods of initial ischemia can still significantly limit infarct expansion. After baseline measurements of hemodynamics, tension-time index, and regional myocardial blood flow in 73 open-chest, adult dogs, the left anterior descending coronary artery was ligated for 15 minutes or 1, 2, 4, or 6 hours of unprotected ischemia. In the five control groups, the initial ischemic period was merely extended for another 4 hours. In the five experimental groups, the animals were placed on pulsatile left atrial-femoral artery bypass for another 4 hours after the initial ischemic period. At the end of each procedure, gentian violet was used to identify the area at risk of infarction, and triphenyltetrazolium chloride was used to delineate the area of infarct. The results showed a significant reduction in the area of infarct as a percentage of the area at risk in each bypass group compared with its control group for all ischemic periods of less than 6 hours. These findings suggest that the maximum permissible ischemic time delay for myocardial salvage by pulsatile left atrial-femoral artery bypass is one which is pertinent in a clinical setting. The results justify continued attempts to develop appropriate techniques for percutaneous application of this modality to patients with an evolving myocardial infarction.

Animals↗
PubMed1985

Analysis of morbidity and mortality in patients 70 years of age and over undergoing isolated coronary artery bypass surgery.

With increasing frequency more elderly patients are referred for coronary artery bypass surgery. The operative results of 201 patients 70 years of age and over were compared with the results of 1242 patients under 70 years operated on since 1981. A larger percentage of the elderly patients had triple-vessel disease (66.2% vs 51.0%, p less than 0.001), left main coronary artery obstruction (34.8% vs 16.3%, p less than 0.01), and an ejection fraction of less than or equal to 45% (30.8% vs 21.1%, p less than 0.001). An increase percentage of the patients 70 years of age and over had perioperative myocardial infarction (7.9% vs 4.1%, p less than 0.05), required prolonged ventilatory support (7.9% vs 3.1%, NS), and had major neurologic complications (4.0% vs 1.1%, p less than 0.001). The mortality rate was significantly higher in the elderly patients (5.9% vs 1.9%, p less than 0.01) but did not correlate with degree of coronary artery disease, anginal pattern, or preoperative ventricular function. Only 2 of 12 deaths in the elderly patients were from cardiac causes. This data would suggest that elderly patients have an increased risk for significant cardiac and noncardiac morbidity and mortality following coronary artery bypass surgery and that the higher mortality rate in this age group may be a result of noncardiac organ failure.

Age Factors↗
PubMed1985

Efficacy of percutaneous transluminal coronary angioplasty compared with single-vessel bypass.

The use of percutaneous transluminal coronary angioplasty has been increasing rapidly. When the procedure is successful, the clinical relief of symptoms is similar to that achieved with direct coronary artery bypass. It has been suggested that the angioplasty procedure, however, can accomplish these results with potentially less morbidity and mortality, along with a shorter hospital stay. In order to evaluate the results of percutaneous transluminal coronary angioplasty with single-vessel coronary artery bypass, we performed a retrospective review. From January, 1982, to December, 1983, a total of 198 angioplasty procedures were performed. They were successful in 142 patients (71.7%). Emergency bypass was performed in 21 (10.6%) of the 56 patients who had undergone unsuccessful angioplasty procedures. Perioperative myocardial infarction occurred in eight of these patients (38.1%). There were no operative deaths, but there was one death after angioplasty. Elective bypass was performed in 28 of the patients who had angioplasty procedures, with no perioperative myocardial infarctions or operative deaths. Recurrent symptoms developed in 31 (21.8%) of the 142 patients who had undergone initially successful angioplasty. From 1982 to 1983, single-vessel bypass was performed in 143 patients. The internal mammary artery was utilized in 102 patients and the autogenous saphenous vein in 41 patients. There were no perioperative myocardial infarctions or deaths. No patients developed recurrent symptoms during the study interval. Percutaneous transluminal coronary angioplasty is an acceptable alternative to coronary artery bypass in patients with localized lesions that are sufficiently serious to cause symptoms and warrant surgical bypass. However, the angioplasty procedure, when compared to single-vessel coronary artery bypass, may result in an increased incidence of acute myocardial infarction and in a significantly (p less than 0.001) increased incidence of early recurrence of symptoms.

Adult↗
PubMed1985

Venoarterial bypass: a technique for spinal cord protection.

In the present study, we examined the effects of various levels of oxygen tension on spinal cord blood flow while using somatosensory evoked potentials to monitor spinal cord sensory function during hypoxia. In this experiment, six adult, mongrel dogs were heparinized and placed on right atrial-femoral artery bypass with an oxygenator in the bypass circuit. The aorta was cross-clamped proximal to the left subclavian artery, and bypass flow and fluid balance were adjusted so as to maintain a distal aortic perfusion pressure of greater than 80 mm Hg. Oxygen flow to the oxygenator was lowered by graded decrements to provide decreasing levels of oxygen tension, which ultimately approached pure venoarterial bypass. Each successive oxygen level was maintained for 30 minutes. Spinal cord blood flow was measured with radioactive microspheres, and latency and amplitude of somatosomatic evolved potentials were continuously monitored. The somatosensory evolved potential signal was invariably present as long as the distal aortic pressure was greater than 80 mm Hg; there were several transient hypotensive episodes (less than 5 minutes), which were accompanied by reversible loss of somatosensory evolved potentials. The spinal cord blood flow increased from 13.6 to 119.7 ml/100 gm/min as the distal oxygen tension fell to a mean value of 30 mm Hg, while latency of somatosensory evolved potentials increased 19.3% and amplitude decreased 43.3%. These results suggest the following conclusions: (1) In response to hypoxia, spinal cord blood flow dramatically increases and somatosensory evolved potentials deteriorate (increase in latency and decrease in amplitude). (2) However, during prolonged hypoxia, spinal cord sensory function can be maintained by sufficiently high flow rates and perfusion pressures. (3) Somatosensory evolved potentials can be used to monitor continuously spinal cord sensory function under these conditions.

Animals↗
PubMed1985

Adjunctive left ventricular unloading during myocardial reperfusion plays a major role in minimizing myocardial infarct size.

Although prompt institution of reperfusion following coronary artery occlusion has been shown to limit myocardial infarct size, significant "reperfusion injury" may result. We investigated in a canine model whether maintenance of the left ventricle in an unloaded state during the initial reperfusion period following acute myocardial ischemia would result in greater limitation of infarct size or modify the development of reperfusion injury. Group I (control, n = 6) underwent 6 hours of occlusion of the left anterior descending coronary artery without further intervention. In both Group II (n = 6) and Group III (n = 6), the snare was released after 2 hours and hearts were reperfused for 4 hours. In Group III only, the left ventricle was maintained in an unloaded state throughout the entire reperfusion interval via pulsatile left atrial-femoral artery bypass. The results showed that reperfusion of the left ventricle in an unloaded state resulted in significantly improved limitation of both infarct size (area of infarct/area at risk = 16.6% for Group III versus 72.0% for Group I and 55.4% for Group II, p less than 0.001) and area of microvascular damage (area of microvascular damage/area at risk = 4.8% for Group III versus 30.6% for Group II, p less than 0.001). These results indicate that although myocardial reperfusion of the type provided by thrombolysis and/or angioplasty techniques does result in limitation of infarct size when compared to no reperfusion, this limitation is not optimal unless the left ventricle is unloaded during the initial reperfusion period.

Animals↗
PubMed1984

Increased release of cyclic adenosine monophosphate into jugular vein in response to isoproterenol administration.

Catecholamine administration elevates plasma cyclic AMP (cAMP) levels but the source of the cAMP is unknown. To determine possible sources, plasma cAMP levels were determined in blood vessels across the head, liver, kidney and lung in anesthetized dogs infused with the beta-adrenergic agonist, isoproterenol. Only the head showed an increased release of cAMP into the blood. The kidneys removed cAMP from the blood while liver and lung showed no change. This in vivo demonstration of release of cAMP from the head represents contributions from brain and facial muscles and may be a useful approach to study brain involvement in the action of various hormones and drugs.

Animals↗
PubMed1984

Prevention of ischemic spinal cord injury following aortic cross-clamping: use of corticosteroids.

Prior to proximal aortic cross-clamping, baseline measurements of spinal cord blood flow and function were done. Blood flow was evaluated with radioactive microspheres and function determined by assessment of somatosensory evoked potential (SEP). Group 1 (N = 6) animals had aortic cross-clamping for 5 minutes after ischemic spinal cord dysfunction (SEP loss) was documented. Group 2 (N = 9) underwent aortic cross-clamping for 10 minutes after loss of SEP. Group 3 (N = 6) also underwent 10 minutes of cross-clamping after initial SEP loss, but were treated intravenously with methylprednisolone (30 mg per kilogram of body weight) 10 minutes prior to cross-clamping and again 4 hours postoperatively. After release of the cross-clamp, the animals were allowed to recover and serial evaluations of spinal cord blood flow and neurological status were carried out for seven days. Group 1 animals recovered uneventfully without evidence of neurological injury. Group 2 animals sustained a 67% incidence of permanent spastic paraplegia (p = 0.02 versus Group 1). In contrast, methylprednisolone-treated animals sustained no clinically detectable neurological injury (p = 0.02 versus Group 2). Measurements of spinal cord blood flow at the time of SEP loss revealed similar degrees of spinal cord ischemia in all groups. No significant differences were observed in the duration of aortic cross-clamping prior to SEP loss among the three groups. The data indicate that short periods of cross-clamping (5 minutes) following SEP loss are well tolerated, whereas longer periods (10 minutes) are associated with a high incidence of paraplegia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1984

Surgical therapy of a dissecting aortic aneurysm involving a right-sided aortic arch.

Dissecting aortic aneurysm involving a right-sided aortic arch is apparently quite rare. A patient with this unusual entity is described. By performing an extraanatomic bypass, the aneurysm was excluded between stainless steel staples. The patient was discharged from the hospital 21 days postoperatively. Although the reasons for the extreme rarity of this entity are not clear, precise anatomic definition is required for successful surgical therapy.

Aortic Dissection↗