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Biomedical subjects

G N Olinger

Publications and source records attributed to G N Olinger.

At least 55 records · Page 3Linked to original sources

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. III. Long-term changes and their modification by platelet inhibition with aspirin and dipyridamole.

The objectives of this study were to elucidate the long-term influence on vein bypass grafts of platelet inhibition and its late discontinuation. Cephalic vein grafts were interposed bilaterally in the femoral arteries of stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Fifteen animals were divided into three groups of five animals each. Group I received no medications and served as a control group. Group II received for the full duration of the study a combination of aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Group III received the same regimen of platelet inhibition as in group II during the first 9 months, but were not treated during the subsequent 9-month interval. Grafts were excised for analysis from groups I and II at both 9 and 18 months and from group III at 18 months. Cholesterol content in group I grafts was 470 +/- 89 micrograms/100 mg at 9 months and 388 +/- 127 micrograms/100 mg at 18 months. In group II grafts, cholesterol content was 208 +/- 72 micrograms/100 mg at 9 months (p less than 0.001 compared with group I) and 266 +/- 84 micrograms/100 mg at 18 months. In group III grafts, cholesterol content was 249 +/- 71 micrograms/100 mg at 18 months. Differences in cholesterol content among the three groups of grafts at 18 months were not found to be statistically significant. Stepwise regression analysis at 18 months showed that cholesterol content was best predicted by medial fibrosis (r2 = 0.66) followed by abundance of foam cells (increase in r2 = 0.26) in group I, by fibrin in group II (r2 = 0.63), and by prevalence of macrophages in group III (r2 = 0.74). In all groups, platelets, fibrin, and polymorphonuclear leukocytes were less abundant than they had been at 3 months. Cross-sectional area occupied by the intima was not influenced by platelet inhibition.

Animals↗

Operative factors, not hemodynamics, modify hormones in repair of coarctation.

This study was designed to evaluate separately the influence of restoration of distal pulse pressure and the influence of factors related to operation upon hemodynamic and hormonal alterations accompanying repair of canine aortic coarctation. Eight normal adult dogs underwent a sham operation and served as controls. In 10 dogs the thoracic aorta was transfected and reanastomosed. In 10 dogs aortic coarctation was created within 1 week of birth by banding the aorta just proximal to the ductus ligament, thereby fixing lumenal diameter at 1 to 2 mm. Studies were performed in the latter animals 18 months after operation. These dogs were subdivided into two groups: one (n = 6) underwent surgical repair of the coarctation; in the other (n = 4), the coarctation was repaired and an occluder was placed on the aorta to maintain distal aortic pulse pressure at its diminished preoperative level. Normal distal pulse pressure was restored in these animals by releasing the occluder 1 week after recovery from the repair of coarctation. Each dog was studied in the conscious state before the definitive procedure and again 24 hr later. Plasma renin activity increased significantly after operation in the sham and in the transection groups. Renin activity and proximal blood pressure were significantly elevated and distal pulse pressure was diminished preoperatively in both the repair and the occluder groups. After their respective definitive procedures, the elevation in renin activity and in proximal pressure persisted in the repair group but decreased in the occluder group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Long-term internal cardiac defibrillation threshold stability.

The automatic implantable cardioverter-defibrillator is tested intraoperatively with defibrillation trials to ensure effectiveness. It is unknown if the energy requirement for internal defibrillation remains stable and that once demonstrated effective, if the device will continue to be effective in terminating lethal ventricular arrhythmias. In this study, the defibrillation energy requirement was compared in 56 patients at the time of lead implantation to that obtained at the time of generator replacement. Mean time to generator replacement was 17. +/- 6.6 months. The defibrillation threshold was stable over that time (11.9 +/- 6.7 joules compared to 12.7 +/- 8.4 joules, NS). There was no relation between transmyocardial impedance and defibrillation threshold. In addition, no effect on defibrillation threshold was demonstrated by the use of various cardiac medications, concomitant surgery or the occurrence of clinical shocks during follow-up.

Electric Countershock↗

A sheath for repetitive insertion of high-fidelity micromanometer-tipped catheters.

Implantation of micromanometer-tipped catheters into dogs and other animals for invasive high-fidelity blood pressure measurement is expensive and impractical. We have devised an implantable sheath that allows insertion of the transducer each time the animal is to be studied. This eliminates animal-inflicted damage and the need for multiple transducers if several animals are to be instrumented concurrently. The sheath is coextruded from hard and soft forms of polyurethane to form a soft, flexible, thrombus-resistant tubing with a hard thin inner lining having a low coefficient of friction. This allows chronic implantation of the sheath into the heart and major vessels with minimal trauma, yet enables a transducer to be advanced through a sheath only slightly larger than the transducer itself without the frictional resistance common to other soft tubing. The sheath can be tapered for ease of implantation into vessels or curved to the appropriate angle for implantation into the heart. Our polyurethane sheath is a versatile, convenient, and inexpensive alternative to chronic instrumentation with transducers for high-fidelity pressure measurement.

Animals↗

Myocardial ischemia and reperfusion: direct evidence for free radical generation by electron spin resonance spectroscopy.

Electron spin resonance spectroscopy has recently been used by others to detect directly radical species in isolated perfused hearts. Sample processing prior to spectroscopy in this study involved pulverization of tissue, which can artifactually generate radical species. We assessed in isolated perfused hearts the influence of tissue pulverization on the identity of radical species detected by spectroscopy and then, using a processing technique less likely to induce artifacts, whether myocardial ischemia and reperfusion generate radical species. Rat and rabbit hearts (n = 8) were perfused aerobically for 10 min and freeze-clamped to -196 degrees C. Frozen tissue was processed at -196 degrees C for spectroscopic analysis by pulverization vs. chopping. Spectra of pulverized tissue consisted of three components: a semiquinone (g = 2.004), a lipid peroxy radical (g [ = 2.04 and g = 2.006), and a carbon-centered radical that is possibly a lipid radical (giso = 2.002 and AHzz approximately equal to 50 G). Chopped tissue consisted of a single component, a semiquinone (g = 2.004). Rat hearts (n = 8 per group) also underwent 10-min global no-flow normothermic ischemia followed by 5-60 sec of either aerobic or anaerobic reperfusion, with frozen tissue chopped prior to spectroscopy. Spectra of ischemic tissue consisted of an iron-sulfur center and a semiquinone. Aerobic reperfusion resulted in a spectrum similar to the control but with increased amplitude that peaked after 10-15 sec of reflow. Anaerobic reperfusion yielded a spectrum identical to that of ischemic tissue. We conclude that pulverization of frozen myocardial tissue arti-factually generates radical species. Using a nonpulverization technique for tissue processing, we found that myocardial ischemia and reperfusion produce radical species but that molecular oxygen is necessary for the burst of radical production during reflow.

Aerobiosis↗

Alpha adrenoceptor subtypes and receptor reserve in human versus canine saphenous vein: sensitivity to blockade by nitroglycerin.

The purpose of this investigation was to determine the subtypes of alpha adrenoceptors present in human saphenous vein and to determine if there is a large receptor reserve for phenylephrine as has been demonstrated in canine saphenous vein. The subtypes of alpha adrenoceptors found in isolated human saphenous vein were determined using selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists. Prazosin, a selective alpha-1 antagonist, produced a parallel shift of the concentration response curve to phenylephrine, a selective alpha-1 agonist, with no significant reduction in the maximal response. Yohimbine, a selective alpha-2 antagonist, produced a parallel shift of the concentration response curve to B-HT 920, a selective alpha-2 agonist, with no reduction in the maximal response. The pA2 values obtained for prazosin and yohimbine in human saphenous vein agreed closely with corresponding values obtained in canine saphenous vein. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors exist in human saphenous vein. Phenoxybenzamine (10(-7) M), an irreversible alpha-1 adrenoceptor antagonist, markedly reduced the maximal response produced by phenylephrine, an agonist with high intrinsic activity, with no significant shift in the concentration response curve in human saphenous vein, suggesting that there was little or no alpha-1 receptor reserve for phenylephrine. The sensitivity of alpha-1 versus alpha-2 adrenoceptor-mediated vasoconstrictor responses to nitroglycerin were compared in human and canine saphenous veins. In both species, nitroglycerin blocked the vasoconstrictor response produced by stimulation of alpha-2 adrenoceptors to the same degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Age-related changes in the ability of hypothermia and cardioplegia to protect ischemic rabbit myocardium.

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children; poor postischemic recovery of function and increased mortality may result when this method of myocardial protection is used in children. The relative susceptibilities to ischemia-induced injury modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused immature (7- to 10-day-old) and mature (6- to 24-month-old) rabbit hearts. Hearts were perfused aerobically with Krebs-Henseleit buffer in the working mode for 30 minutes, and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2, followed by hypothermic (14 degrees C) global ischemia (mature hearts 2 and 4 hours; immature hearts 2, 4, and 6 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic function was measured. Hypothermia alone provided excellent protection of the ischemic immature rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 97% +/- 3% and 93% +/- 4% (mean +/- standard deviation) of the preischemic value. Mature hearts protected with hypothermia alone recovered only minimally, with 22% +/- 16% recovery of preischemic aortic flow after 2 hours; none were able to generate flow at 4 hours. St. Thomas' Hospital solution No. 2 improved postischemic recovery of aortic flow after 2 hours of ischemia in mature hearts from 22% +/- 16% to 65% +/- 6% (p less than 0.05), but actually decreased postischemic aortic flow in immature hearts from 97% +/- 3% to 86% +/- 10% (p less than 0.05). To investigate any dose-dependency of this effect, we subjected hearts from both age groups to reperfusion with either Krebs solution or St. Thomas' Hospital solution No. 2 for 3 minutes every 30 minutes throughout a 2-hour period of ischemia. Reexposure to Krebs solution during ischemia did not affect postischemic function in either age group. Reexposure of immature hearts to St. Thomas' Hospital solution No. 2 caused a decremental loss of postischemic function in contrast to incremental protection with multidose cardioplegia in the mature heart. We conclude that immature rabbit hearts are significantly more tolerant of ischemic injury than mature rabbit hearts and that, unexpectedly, St. Thomas' Hospital solution No. 2 damages immature rabbit hearts.

Aging↗

Delayed infection of the automatic implantable cardioverter-defibrillator. Current recognition and management.

Three cases of delayed infection of automatic implantable cardioverter-defibrillator devices without systemic manifestations are reported. Computed tomographic scan of the heart revealed fluid deep to the patch in each case. Sonication of explanted automatic implantable cardioverter-defibrillator patches facilitated the recovery of adherent microorganisms in one case. Management of this previously unrecognized problem is outlined.

Aged↗

Stratified application of the automatic implantable cardioverter defibrillator.

Since June 1983 we have developed a stratified regimen for staged implantation of the automatic implantable cardioverter defibrillator system. The protocol for management in patients who have fully recovered from sudden cardiac death is initiated with the use of standard electrophysiologic evaluation. Treatment in order of application has consisted of drugs followed by implantation of the device for patients with drug-refractory arrhythmias in whom direct cardiac surgical intervention for anatomic substrates for sudden death are absent. In surgical candidates, combinations of coronary revascularization and ablative therapy have been used to mitigrate the potential for lethal arrhythmia. Sensing and defibrillator lead systems have been placed at corrective operations to be followed later by implantation of the cardioverter defibrillator generator for either inducible or spontaneous tachyarrhythmia. This staged application has been effective in markedly reducing actual sudden cardiac death while at the same time saving on unnecessary device implantation. Morbidity of lead implantation alone remains a concern, particularly for infective complications. Additional follow-up is required to assess the validity of this approach.

Anti-Arrhythmia Agents↗

Primary repair of acute ascending aortic dissection.

Primary repair of acute ascending aortic dissection was performed in 14 patients. Repair included resection of the intimal tear where applicable, a circumferential suture line in the ascending aorta at the site of the tear, and wrapping of the intrapericardial ascending aorta with Teflon felt to contain the distal residual false channel. The aortic valve was resuspended in 6 patients. The single operative death was unrelated to the method of repair. Two late deaths at 4 and 6 years were due to preexisting multisystem disease. In 1 patient, new aortic insufficiency with an isolated aneurysm of the noncoronary sinus of Valsalva developed at 26 months, and was repaired successfully at another institution. These results compare favorably with those reported by others employing more extensive surgical procedures for repair of acute ascending aortic dissection.

Acute Disease↗

Hemodynamic and hormonal abnormalities in canine aortic coarctation at rest and during exercise.

This study was designed to determine the hemodynamic and hormonal consequences of aortic coarctation at rest and during treadmill exercise. Twelve normal adult dogs served as controls. In eight dogs coarctation was created within 1 week of birth by banding the aorta just proximal to the ductus ligament, thereby fixing luminal diameter at 1 to 2 mm. Studies were performed 18 months after operation. Vascular pressures were monitored proximal and distal to the coarctation, cardiac output and regional blood flow were evaluated with radioactive microspheres and blood samples were collected for determination of hormone levels and blood gases. At rest, systolic pressure in the proximal aorta was 130 +/- 12 mm Hg (mean +/- SD) in the control group and 167 +/- 16 mm Hg in dogs with coarctation (p less than 0.01). During exercise at a level that doubled heart rate and cardiac index, mean aortic pressure increased by 11 and 31% (p less than 0.01) in the control and the coarctation group, respectively. Mean distal aortic pressure increased by 8% during exercise in control dogs but decreased by 29% in dogs with coarctation. Exercise decreased flow to the kidneys and the large intestine in the coarctation group. Plasma norepinephrine concentrations were greater in the coarctation group than in control dogs at rest; during exercise, plasma norepinephrine, epinephrine and renin activity increased in both groups, but to a greater degree in the group with coarctation. These results confirm an abnormality in renal and gut perfusion in experimental coarctation and suggest that this may be related to a decline in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Constrictive pericarditis associated with patch electrodes of the automatic implantable cardioverter-defibrillator.

A case of constrictive pericarditis intimately involving patch electrodes of the automatic implantable cardioverter-defibrillator is described. Typical clinical and hemodynamic findings for constrictive pericarditis were noted 15 months after lead installation. Additionally, chest x-ray examination revealed a severe crumpling deformity of the patch electrodes. Thoracotomy was performed and revealed marked fibrous reaction surrounding both surfaces of each patch electrode. Histologic examination revealed fibrous tissue with multinucleated giant cells, consistent with a foreign body reaction. The patient had complete resolution of signs and symptoms of constrictive pericarditis after removal of the patch electrodes and pericardial stripping. Constrictive pericarditis from implanted patch electrodes appears to be an uncommon complication of the automatic implantable cardioverter-defibrillator and should be considered in patients with one or more patch electrodes and other signs of constrictive pericarditis.

Aged↗

Low-dose aspirin protects against lipid accumulation in primate vein bypass grafts.

Platelet inhibition with high-dose aspirin combined with dipyridamole reduces lipid accumulation and improves early patency of coronary artery bypass grafts. However, recent evidence suggests that platelet inhibition can be achieved with substantially lower aspirin doses than have been conventionally prescribed. To evaluate whether low-dose aspirin protects against lipid accumulation in bypass grafts, we studied 15 stump-tailed macaque monkeys in which autologous cephalic veins were grafted into the femoral arteries. A control group received no treatment, a second group was treated with a low, single daily dose of aspirin (12 mg), and a third group was given a higher dosage of aspirin (80 mg/day) combined with dipyridamole (50 mg/day) divided into two daily doses. A special diet was fed that resulted in plasma cholesterol levels (224 +/- 50 mg/dl, mean +/- standard deviation) and plasma lipoprotein distributions that mimic the profile in humans. Cholesterol concentration in grafts removed 3 months after insertion was 0.47 +/- 0.12 mg/100 mg tissue in the control group; it was reduced to 0.23 +/- 0.04 mg/100 mg (p less than 0.001) by low-dose aspirin and to 0.17 +/- 0.05 mg/100 mg (p less than 0.001) by combined aspirin and dipyridamole therapy. Graft apolipoprotein B concentration was 66 +/- 19 micrograms/100 mg in control group; it was reduced to 40 +/- 8 micrograms/100 mg (p less than 0.05) by low-dose aspirin and to 23 +/- 7 micrograms/100 mg (p less than 0.001) with the combination treatment. There were no differences between groups in either cholesterol concentration (0.09 +/- 0.02 mg/100 mg) or apolipoprotein B concentration (10 +/- 3 micrograms/100 mg) in normal ungrafted vein. Platelet function tests demonstrated platelet aggregation in all control monkeys, in none of the combined therapy group, and in two of five monkeys receiving low-dose aspirin. This study indicates that low-dose aspirin is protective against graft lipid accumulation in monkeys. The mechanism of this antilipid effect and its relation to any antithrombotic effect remain to be elucidated.

Animals↗

Multiple paradoxical emboli.

We report a case of multiple paradoxical emboli involving the common carotid, right subclavian, right renal, celiac, and superior mesenteric arteries. Paradoxical embolus is an uncommon but important cause of acute arterial occlusion. Successful management requires prompt recognition, prevention of further embolization, and treatment directed toward relief of the acute arterial occlusion.

Adult↗