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Biomedical subjects

V A Subramanian

Publications and source records attributed to V A Subramanian.

At least 37 records · Page 2Linked to original sources

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↗

Functional endothelial damage by high-potassium cardioplegic solutions to saphenous vein bypass grafts.

High-potassium cardioplegic solutions (CSs) may induce endothelial cell damage in vascular grafts, promoting graft thrombosis after coronary bypass operations. We studied prostacyclin (PGI2) production by saphenous veins as a marker of endothelial cell function in a model mimicking actual operative conditions. Fresh saphenous vein segments from patients who had undergone coronary bypass were cut in half; each part was perfused and incubated sequentially with CS (with 20, 40, or 80 mEq potassium/L) or a control buffer (5 mEq potassium/L) at 4 degrees C for 30 minutes (perfusion I), buffer at 37 degrees C for 15 minutes (perfusion II), and buffer plus 25 microM sodium arachidonate at 37 degrees C for 15 minutes (perfusion III). This permitted evaluation of changes in PGI2 production during or after exposure to CS, in basal and stimulated conditions. CS with 20 mEq potassium/L did not alter PGI2 production as compared with control buffer. CS with 40 mEq potassium/L decreased PGI2 production during perfusions I and II. CS with 80 mEq potassium/L also decreased sodium arachidonate-stimulated PGI2 production. Endothelial coverage (immunoperoxidase staining for factor VIII antigen) was intact at all potassium concentrations tested. Thus potassium in CSs can depress endothelial PGI2 production without causing immediate endothelial detachment. This effect may favor thrombosis in bypass grafts.

Arachidonic Acids↗

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↗

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↗

Complications of percutaneous intraaortic balloon pumping.

Eight-nine consecutive patients who were considered candidates for counterpulsation were reviewed for complications of the percutaneous intraaortic balloon pump (PIABP). Indications for counterpulsation were cardiogenic shock in 37 patients, refractory ischemia in 35, postcardiotomy shock in nine, acute infarction with threatened extension in four, septic shock in three and elective preoperative use in one patient. In 67 patients (75.3%), successful passage of the balloon was accomplished in a single attempt; the opposite-side attempt was successful in 10 patients (11.2%) and neither attempt was successful in 12 (13.5%). Seventy-seven patients who underwent PIABP had major complications, including limb ischemia in 12, bleeding at the puncture site in three, permanent foot drop in three, aortic dissection in three, renal embolism in one and false aneurysm at the puncture site in one. Fourteen patients had minor complications: asymptomatic loss of pedal pulses in eight, transient bacteremia in two, parasthesias in two and wound hematoma in two. No patient had free perforation, balloon rupture or wound infection. The rate and severity of complications of PIABP are similar to those with conventional IABP insertion. Ease of insertion alone should not be grounds for using PIABP in patients who can be managed without counterpulsation.

Aortic Rupture↗

Simplified technique for intraaortic balloon insertion.

A simple technique for insertion and removal of an intraaortic balloon catheter is described. We have used it in 20 patients in the past six months, and the incidence of thrombi around the junction of the Dacron patch and the artery has been lessened. The prsence of a foreign body can be avoided also. We have not encountered any incidence or regional vascular compromise.

Assisted Circulation↗

Advantages of hypothermic potassium cardioplegia and superiority of continuous versus intermittent aortic cross-clamping.

The relative effectivenss of hypothermic potassium (K) cardioplegia in conjunction with either continuous or intermittent aortic cross-clamping was evaluated in 20 mongrel dogs. Isovolumetric left ventricular (LV) contractions and myocardial biopsies were obtained before and after a total of 90 minutes of aortic cross-clamping. The dogs were randomly divided into four groups of five dogs each as follows: Group I, continuous 90 minute cross-clamping and multidose K at 4 degrees C (40 mEq/L); Group II, intermittent cross-clamping consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and K cardioplegia at 4 degrees C given at the start of each cross-clamping period; Group III, continuous 90 minute cross-clamping and multidose buffered saline at 4 degrees C; Group IV, intermittent cross-clamping, consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and buffered saline at 4 degrees C given at the initiation of each cross-clamp period. Group I dogs had the best myocardial performance, with no difference between control values of peak LV pressure and dP/dtmax and those recordings obtained 60 minutes after release of the aortic cross-clamp. Significant depression of LV function was noted in all other groups. Examination of force-velocity and length-tension relationships confirmed better myocardial performance in Groups I and II (multidose K at 4 degrees C) than in Groups III and IV (buffered saline at 4 degrees C). Groups I and III (continuous cross-clamping) had no de-rease in diastolic LV compliance after cross-clamping, whereas compliance was decreased in both Groups II and IV (intermittent cross-clamping) at higher preloads (p less than 0.05 and p less than 0.025, respectively). The wet weight/dry weight myocardial ratios were lower in Groups I and III (continuous cross-clamping) than in Groups II and IV (intermittent cross-clamping). Although creatine phosphate (CP) concentrations were rapidly restored by reperfusion in all groups, adenosine triphosphate (ATP) and glycogen myocardial stores were better preserved at the end of cross-clamping in Groups I and II (multidose K at 4 degrees C). Although LV diastolic compliance was decreased and myocardial water content was increased in Groups II and IV (intermittent cross-clamping), no differences in the minimal extent of subendocardial hemorrhage, edema, and contraction-band necrosis were observed among any of the groups examined electron microscopically. The present study identifies continuous aortic cross-clamping with multidose K at 4 degrees C as a superior method of myocardial protection.

Animals↗

Perioperative myocardial infarction associated with coronary artery bypass graft surgery: improved sensitivity in the diagnosis within 6 hours after operation with 99mTc-glucoheptonate myocardial imaging and myocardial-specific isoenzymes.

The present study was performed to evaluate scintigraphic imaging with technetium 99m-labeled glucoheptonate and serum enzyme levels of creatine phosphokinase isoenzyme (MB-CPK) in the early diagnosis of perioperative acute myocardial infarction associated with saphenous vein bypass graft operations. Myocardial imaging was done in 27 patients (50% of whom were considered high-risk) before operation and again 5 hours after operation. Four of these patients (15%) had both electrocardiographic and serum MB-CPK evidence of acute myocardial infarction, and all 4 had developed positive postoperative scintigrams. Four other patients had only elevated serum MB-CPK, and scintigrams became positive after operation in 3 of them. In addition, serum MB-CPK 6 hours after operation was 83 +/- 21 mIU/ml (mean +/- standard error of the mean) in patients with positive postoperative scans compared with 24 +/- 5 mIU/ml in those patients with negative postoperative scintigrams (p less than 0.001). Myocardial imaging with 99mTc-glucoheptonate in the perioperative period is rapid, safe, and atraumatic. Furthermore, our results suggest that it is a sensitive method for the early diagnosis of perioperative acute myocardial infarction, and, when imaging is combined with serum MB-CPK isoenzyme analysis, the reliability of the diagnosis of acute myocardial infarction is enhanced even further. Only 1 of the patients who showed perioperative myocardial damage had acute hemodynamic compromise or obvious impairment of recovery in the immediate postoperative period, and the 30-day mortality of the total group was 4% (1 of 27).

Acute Disease↗

Atrial myxoma mimicking a collagen disorder.

A 14-year-old boy had a protracted illness characterized by bilateral tenderness and weakness of the extremities; the illness was considered to be a connective tissue disease similar to polymyositis. Not until nine months later, when the patient had new cardiac murmurs, pulmonary edema, and then a cerebrovascular accident, was the true nature of his illness suspected. The diagnosis of left atrial myxoma with the triad of constitutional, obstructive, and embolic effects was confirmed by echocardiographic studies and cardiac catheterization. The tumor was successfully removed.

Adolescent↗

A rat model for study of bilirubin conjugation by a cultured cell/ artificial capillary liver assist device.

The Gunn rat, congenitally lacking the conjugating enzyme glucuronyl transferase, provides an animal model for the study of bilirubin conjugation by an extracorporeal liver assist device (LAD) composed of cultured cells and artificial capillaries. Rat hepatoma cells of the H4-II-E cell line able to form conjugated bilirubin glucuronide from bilirubin were grown to tissue density by circumfusion culture of the LAD before symbiotic hemoperfusion experiments lasting up to 24 hours. Rat bile was analyzed by thin layer chromatography for bilirubin glucuronide which was formed by the device and then excreted by the rat.

Acrylic Resins↗

Role of delayed intraaortic balloon pumping in treatment of experimental myocardial infarction.

Intraaortic balloon pumping improves coronary blood flow characteristics while simultaneously reducing myocardial oxygen demands by reducing aortic systolic pressure. Clinical application of intraaortic balloon pumping has largely been in the "high risk" patient (cardiogenic shock, postinfarction angina, left main coronary artery disease and unstable angina) for support during diagnostic studies or cardiac surgery, or both. In addition, there is some evidence that balloon pumping immediately after coronary occlusion reduces the size of experimentally induced myocardial infarcts. In this study, myocardial infarcts were produced by ligation of the left anterior descending coronary artery in 12 dogs, 6 of which were treated with balloon counterpulsation beginning 3 hours after coronary occlusion. All dogs were killed 8 hours after coronary ligation. Intraaortic balloon pumping resulted in the expected hemodynamic changes (decreased aortic systolic pressure, left ventricular end-diastolic pressure and heart rate and increased aortic peak diastolic pressure). In addition, there was a significant reduction in infarct size in the group with balloon pumping as determined with epicardial S-T segment mapping, myocardial imaging with technetium-99m-glucoheptonate and histochemical staining with nitroblue tetrazolium. These results suggest that even when instituted as long as 3 hours after coronary occlusion, intraaortic balloon pumping results in significant reduction in infarct size and, it might be speculated, the mortality and morbidity associated with acute myocardial infarction may also be decreased.

Angina Pectoris↗