Search PubMed⌕ Search

Biomedical subjects

W A Gay

Publications and source records attributed to W A Gay.

At least 55 records · Page 3Linked to original sources
PubMed1987

Treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody.

OKT3 monoclonal antibody is a murine monoclonal antibody specific for the T lymphocyte T3 cell surface receptor that mediates antigen recognition. The use of OKT3 monoclonal antibody for the treatment of cardiac allograft rejection refractory to conventional therapy with high-dose steroids and antithymocyte globulin is described. Seven patients received 5 mg of OKT3 monoclonal antibody intravenously per day for 10 to 14 days. Diagnosis of moderate or severe rejection was made in all seven from right ventricular endomyocardial biopsy. Biopsy was repeated 48 to 72 hours and seven to 10 days after OKT3 monoclonal antibody was begun. With treatment, four patients had a complete response, with improvement on both early and late biopsy. Two patients had partial responses, with improvement on early biopsy followed by worsening rejection on late biopsy. One patient died of graft failure six hours after receiving OKT3 monoclonal antibody. Adverse events were common in the first two days of therapy but were well tolerated. It is concluded that OKT3 monoclonal antibody is useful in the treatment of refractory cardiac allograft rejection.

Adult↗
PubMed1987

Age-associated decline in cardiac allograft rejection.

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.

Actuarial Analysis↗
PubMed1987

Effect of preoperative antiplatelet drugs on vascular prostacyclin synthesis.

Patients undergoing aortocoronary bypass using autogenous saphenous veins were randomly divided into three comparable groups. Group 1 (n = 10) acted as a control, Group 2 (n = 14) received 80 mg of aspirin at midnight before the operation, and Group 3 (n = 12) received 80 mg of aspirin and 75 mg of dipyridamole at midnight and an additional 75-mg dose of dipyridamole at 6 AM. The purpose was to determine which regimen would maximally inhibit platelet function without depressing vascular prostacyclin synthesis. Serum thromboxane A2, saphenous vein wall and aortic wall prostacyclin, platelet aggregation, and bleeding time were measured in all patients. None was restarted on a regimen of aspirin or dipyridamole postoperatively. Aspirin alone and in combination with dipyridamole significantly inhibited thromboxane A2 and platelet aggregation in all treated patients but spared venous prostacyclin synthesis. Aortic prostacyclin synthesis was partially inhibited in both treated groups. Chest tube drainage was comparable in all three groups. These results indicate that the combination of aspirin and dipyridamole offers no measurable advantage over aspirin alone in the perioperative period.

Aspirin↗
PubMed1987

Survival following cardiac transplantation--what are acceptable standards?

In an 18-month period, 50 orthotopic cardiac transplantations were done in Utah in 48 patients with end-stage heart failure. The 12-month actuarial survival was 98%, indicating that successful cardiac transplantation can be done in a newly established program and that the intermountain West has an adequate supply of potential recipients and donors for a moderate- to high-volume program. Furthermore, the administration of cardiac transplantation in a setting of other treatment modalities of heart failure in a multi-institutional program that crosses private practice-academic barriers is feasible. Results such as these need to be considered by the federal government as it establishes eligibility criteria for centers to be approved for Medicare-funded cardiac transplantation.

Actuarial Analysis↗
PubMed1986

IgE-mediated hypersensitivity in human heart tissue: histamine release and functional changes.

In experiments described herein, it was observed that IgE-mediated hypersensitivity can result in significant histamine and thromboxane release from human myocardium, suggesting that the human heart may participate as a target organ in allergic reactions. Muscle units (pectinate muscles) were isolated from human atrial appendages, removed routinely during corrective cardiac surgery, and were allowed to beat spontaneously in a tissue bath. Remnants of each atrial specimen were chopped and added to the tissue bath. Challenge of the atrial tissue with goat antiserum to human myeloma IgE caused histamine and thromboxane B2 release and marked increases in contractility and spontaneous rate. In contrast, challenge with nonspecific goat antiserum or with antiserum from which anti-IgE antibodies had been removed caused neither mediator release nor changes in rate or contractility. The histamine H2-receptor antagonist cimetidine inhibited the inotropic and chronotropic changes but not the histamine release.

Adult↗
PubMed1986

Postpneumonectomy tension chylothorax.

Chylous leak from the thoracic duct into the pleural space may occur after any type of thoracic surgery. This is a serious, often life-threatening entity. Two cases of postpneumonectomy chylothorax with hemodynamic compromise are reported. Early recognition, pathophysiology, and optimal management of this problem are discussed.

Aged↗
PubMed1985

Early infarct expansion: structural or functional?

With the onset of ischemia, the length of myocardial segments increases rapidly, distorting ventricular geometry. Permanent stretching and thinning of infarcted zones have been termed infarct expansion. Although these changes are noted within minutes in vivo, infarct expansion may not be seen for days in postmortem preparations. The apparent postmortem reversal of early infarct expansion suggests that early expansion may be a functional phenomenon, reversible in the early hours of infarction. Alternatively, reversal of expansion may be a postmortem artifact, concealing the importance of underlying structural abnormalities. Myocardial infarction was produced in five dogs by occluding the left anterior descending coronary artery. Ultrasound sonomicrometers were used to measure myocardial segment end-diastolic length in the infarct and normal zones. After 3 hours of ischemia, the heart was arrested in diastole and biopsy specimens were taken from the normal and infarct zones. Sarcomere length was measured from electron photomicrographs, and myofiber width was measured from light photomicrographs. After 3 hours of ischemia, infarct zone segment length had increased significantly more than normal zone length (116 +/- 11 [SD] versus 103 +/- 4% of control length, p less than 0.05), whereas 2 minutes after cardiac arrest, both the infarct and normal zones returned to preischemic segment length, demonstrating apparent reversibility of early infarct expansion. However, histologic study revealed that the infarct zone myofibers were significantly thinner than normal zone myofibers (7.9 +/- 0.3 versus 9.4 +/- 0.3 micron, p less than 0.001) and sarcomere length in the infarct zone was significantly longer than that in the normal zone (1.9 +/- 0.2 versus 1.5 +/- 0.2 micron, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Glutaraldehyde-preserved pericardial allografts for pericardial closure.

Repeat cardiac surgery is significantly more difficult than the original surgery. Pericardial closure to limit adhesion formation between the heart and mediastinal structures and thus reduce the increased difficulty of reoperation has been considered. To investigate the feasibility of effecting loose pericardial closure with homologous pericardial grafts, glutaraldehyde-preserved pericardial allografts were implanted in 10 mongrel dogs. After a mean period of 6.7 months (range 6 to 8 months) the grafts were studied grossly and histologically. Adhesion formation was minimal and the adhesions were easily dissectible. The allografts evoked no significant inflammatory response. No infections resulted from graft placement. It is concluded that glutaraldehyde-preserved pericardial allografts may be useful to effect pericardial closure and deserve further investigation in this regard.

Animals↗
PubMed1983

Differential inhibition by aspirin of vascular and platelet prostaglandin synthesis in atherosclerotic patients.

We studied the ability of a single oral dose of aspirin to inhibit prostacyclin synthesis by human arterial and venous tissue and to inhibit thromboxane A2 synthesis by platelets in 70 patients who were undergoing aortocoronary bypass. A dose of 40, 80, or 325 mg of aspirin was administered 12 to 16 hours before surgery. The generation of thromboxane in serum--which provides an estimate of platelet thromboxane production--was reduced from the control value by 77, 95, and 99 per cent after single doses of 40, 80, and 325 mg of aspirin, respectively. By contrast, prostacyclin production in aortic tissue that was removed at operation was reduced by only 35, 38, and 75 per cent, respectively, in response to these doses. Production of prostacyclin in saphenous-vein tissue (not tested after 40 mg of aspirin) fell only slightly and not significantly after 80 mg but was reduced by 85 per cent after 325 mg. These findings indicate that a low dose of aspirin (40 to 80 mg) can largely inhibit platelet aggregation and thromboxane synthesis but has much less effect on prostacyclin production in arterial and venous endothelium.

Administration, Oral↗
PubMed1983

The isolated human pectinate muscle: a reliable preparation of human cardiac tissue.

We have developed an anatomically and functionally intact preparation of isolated pectinate muscles from readily-available surgical specimens of human right atrial appendage. Individual pectinate muscles (2-3 per specimen) are dissected free and mounted in a tissue bath. Field stimulation is used for electrical pacing, and isometric contractions are recorded. The pectinate muscle develops a stable and large force of contraction and hence is superior to strips cut from atrial appendage specimens. Isolated pectinate muscles develop spontaneous beating or can be induced to beat spontaneously by brief periods of electrical pacing or transient exposure to epinephrine or histamine. Spontaneously-beating muscles increase their rate and force of contraction in response to drugs which have positive chronotropic and inotropic effects in the whole heart. Because the force of contraction of the pectinate muscle is a function of the rate of beating, inotropic effects of agents should also be evaluated in preparations which are electrically paced at a constant rate.

Atrial Function↗
PubMed1982

Dysrhythmias caused by histamine release in guinea pig and human hearts.

Histamine is released into the systemic circulation during anaphylaxis, by drugs and by surgical procedures. Studies in animal models have conclusively demonstrated that released cardiac histamine is a major mediator of arrhythmias that occur during anaphylaxis and following the administration of histamine-releasing drugs. Several lines of evidence suggest a similar arrhythmogenic role for cardiac histamine in humans: (1) The human heart is rich in histamine; (2) cardiac histamine can be readily released from human heart in vitro by therapeutic concentrations of drugs; (3) histamine has potent arrhythmogenic effects on the human heart in vitro. Arrhythmogenic effects of histamine include enhancement of normal automaticity, induction of abnormal automaticity, induction of triggered tachyarrhythmias, depression of atrioventricular conduction, and increase in the vulnerability of the ventricles to fibrillation. A combination of H1 and H2 antihistamines is needed to block the arrhythmogenic effects of histamine. Certain arrhythmogenic effects of histamine (e.g. induction of slow responses and delayed afterdepolarizations) can also be blocked by drugs which inhibit the influx of cations through slow channels. In contrast, the commonly-used drug digitalis potentiates the arrhythmogenic effects of histamine. We propose that histamine release produced by drugs and surgical procedures may be an overlooked factor in fatal cardiac arrhythmias. Experimental studies suggest that selective pharmacological methods can be developed to block the arrhythmogenic effects of histamine.

Animals↗
PubMed1981

Prostacyclin production by arterialized autogenous venous grafts in dogs.

Arteries are capable of producing significantly larger quantities of prostacyclin than are veins. To test the hypothesis, whether prostacyclin production by the vessel wall is related to blood pressure and flow, we measured the amounts of PGI2 released and synthesized by venous segments transplanted for 6 weeks into the arterial circulation. These results were compared with the production of prostacyclin by normal veins and arteries. In 20 dogs a segment of jugular vein was interposed into the carotid system; a sham dissection was done on the opposite side. "Arterialized" vein grafts showed prominent intima lined by endothelium, medial smooth muscle cell proliferation and fibrotic proliferation in adventitia. Spontaneous and arachidonic acid-stimulated prostacyclin production (measured by radioimmunoassay for 6-keto-PGF1 alpha) was not significantly different between arterialized venous autografts and jugular veins. Significantly larger amounts of prostacyclin were synthesized by the carotid artery. Thus, histologic changes and rheologic effects occurring in vein grafts transposed to the arterial site do not affect prostacyclin production.

Animals↗
PubMed1981

The effects of crystalloid potassium cardioplegic solution on arterialized canine vein grafts. Assessment of chronic prostacyclin production and histopathologic alterations.

Efforts to improve myocardial preservation during aortocoronary bypass procedures have led to the perfusion of saphenous vein segments with potassium cardioplegic (KCP) solutions after completion of the distal anastomosis. Recent reports show that the procurement of veins leads to varying degrees of damage, particularly to the endothelial surface, as a result of the dissection itself, the hydrostatic pressure required to distend the veins in obtaining hemostasis and the composition of the solutions used to irrigate the harvested segments. The biologic activity of arterialized vein segments is largely unknown. We tested the hypothesis that the degree of venous injury inherent in vein harvesting may be compounded by perfusion with a potassium-rich solution, a known vascular irritant. The external jugular vein was removed from 18 dogs. Half of the vein was perfused with 300 ml of a KCP solution at 4 degrees C (40 mEq/l KCl, 10 ml sodium bicarbonate, pH 7.6, osmolarity 340 mosmol) and the other half with lactated Ringer's solution (LR). The treated vein was reversed and interposed into the excluded internal carotid circulation. A sham dissection was done on the opposite jugular vein. The veins were harvested after 6 weeks and assayed for spontaneous and arachidonate-stimulated (AS) prostacyclin activity as well as light microscopic analysis of morphologic changes. Spontaneous and AS production of prostacyclin did not differ significantly in the sham, LR and KCP groups: 1539 +/- 709 and 4166 +/- 1802, 1569 +/- 763 and 3767 +/- 2706, 1860 +/- 1233 and 3947 +/- 3347 pg/ml). Light microscopic analysis revealed an intense adventitial fibrotic reaction in the KCP group and the appearance of fibroblast-like cells in the outer layer of the vein wall. The intima was intact in all three groups. We conclude that intimal damage sustained during harvesting is repaired within 6 weeks, and there is no impairment to surface production of prostacyclin. The intense adventitial fibrotic reaction observed in the KCP-treated group has not been previously reported, and its significance remains unexplained.

6-Ketoprostaglandin F1 alpha↗