Search PubMed⌕ Search

Biomedical subjects

S Kaul

Publications and source records attributed to S Kaul.

At least 271 records · Page 15Linked to original sources

Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function.

BACKGROUND: Although many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD. METHODS AND RESULTS: Twenty-one patients (mean LV ejection fraction, 0.27 +/- 0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic segments were classified with normal or mildly reduced viability. Among akinetic or dyskinetic segments, 20% had normal 201Tl uptake, 53% had mildly reduced viability, and only 27% had severely reduced viability. 201Tl viability criteria identified segments that improved function after CABG. Sixty-two percent of severely asynergic segments with normal viability and 54% with mildly reduced viability improved function after surgery, but only 23% with severely reduced viability improved function (p = 0.002). When only adequately revascularized segments were considered, the predictive value of a positive preoperative viability scan for functional improvement was 73%. The greatest improvement in global LV function after CABG occurred in patients with the greatest number of asynergic segments classified as viable before surgery (p < 0.01). In 10 patients with more than seven viable, asynergic segments, mean LV ejection fraction increased significantly after CABG (0.29 +/- 0.07 to 0.41 +/- 0.11, p = 0.002). In 11 patients with seven or fewer viable, asynergic segments, mean LV ejection fraction remained unchanged after revascularization (0.27 +/- 0.05 to 0.30 +/- 0.08, p = NS). CONCLUSIONS: In patients with CAD and severely depressed LV function, preoperative quantitative planar rest-redistribution. 201Tl imaging identifies viability in many asynergic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous asynergic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery.

Aged↗

Assessment of risk area during coronary occlusion and infarct size after reperfusion with myocardial contrast echocardiography using left and right atrial injections of contrast.

BACKGROUND: Myocardial opacification during echocardiography has been demonstrated after left (LA) and right (RA) atrial injections of contrast, and microvascular damage with reduced blood flow and impaired flow reserve has been documented in necrotic myocardial tissue. Therefore, we hypothesized that because of its ability to depict capillary perfusion, myocardial contrast echocardiography (MCE) can be used to define risk area during coronary occlusion and infarct size after reperfusion with LA and RA injections of contrast in the presence of pharmacologically induced coronary hyperemia. METHODS AND RESULTS: Eighteen open-chest anesthetized dogs with 3 to 6 hours of left anterior descending artery occlusion and 15 minutes of reflow were studied in the presence of either dipyridamole (0.56 mg/kg over a period of 4 minutes) or dobutamine (15 micrograms.kg-1.min-1). Technetium autoradiography was performed for risk area assessment; infarct size was measured with triphenyl tetrazolium chloride; and in 11 dogs, myocardial blood flow was measured with radiolabeled microspheres. A close linear relation was noted between the MCE defect size and autoradiographic risk area during coronary occlusion both during LA (y = 0.95x-0.25, r = .97, P < .001) and RA (y = 0.90x+0.98, r = .86, P < .001) injections of contrast. During reperfusion, the contrast defect size on MCE was always less transmural than during occlusion and correlated closely with infarct size during both LA (y = 1.07x-2.37, r = .98, P < .001) and RA (y = 1.02x-0.61, r = .95, P < .001) injections of contrast. In the 11 dogs in whom radiolabeled microsphere-derived blood flow was measured during reperfusion, an inverse relation was noted between infarct size and transmural blood flow (y = -1.12x+121, r = -.95, P = .001), implying that MCE defects after reperfusion indicate necrotic regions with reduced blood flow or impaired microvascular flow reserve. A close linear relation (y = 0.79x-0.001, r = .98, P < .001) was also noted between endocardial/epicardial ratio of background-subtracted peak video intensity on MCE and endocardial/epicardial blood flow ratio in the eight dogs with infarction who underwent this measurement after reperfusion. CONCLUSIONS: MCE performed with LA and RA injections of contrast in the presence of pharmacologically induced coronary hyperemia can be used to determine, in vivo, the risk area during coronary occlusion and infarct size after reperfusion. These results could have important implications in this era of myocardial reperfusion.

Animals↗

Characterization of spatial patterns of flow within the reperfused myocardium by myocardial contrast echocardiography. Implications in determining extent of myocardial salvage.

BACKGROUND: Since myocardial blood flow changes dynamically after reperfusion and since both hyperemia and impairment in microvascular function exist within the acutely reperfused bed, we sought to investigate the role of myocardial contrast echocardiography (MCE) in (1) defining the temporal variability in perfusion patterns after reflow and relating these to microsphere-derived blood flow; (2) differentiating viable from infarcted tissue during different periods of reflow; and (3) defining spatial perfusion patterns within the infarct bed in response to exogenously induced maximal vasodilation and relating these to infarct size and extent of myocardial salvage. METHODS AND RESULTS: Twenty-one dogs with 3 hours of left anterior descending coronary artery occlusion and 2 to 3 hours of reflow were studied. MCE was performed at 15 and 45 minutes and 2 and 3 hours after reflow. It was also performed at either 2 or 3 hours after reflow in the presence of 0.56 mg/kg of dipyridamole. Radiolabeled microsphere-derived blood flow was measured at 15 minutes and 2 and 3 hours after reflow and during dipyridamole effect. Infarct size was measured at the end of the experiment by use of triphenyl tetrazolium chloride. MCE data were processed with color-coding schemes that highlighted differences in myocardial videointensities in proportion to the concentration of microbubbles within the microvasculature. There was significant variability in MCE-defined perfusion patterns after reflow, with contrast defects noted mainly within the endocardium. There were fair and significant (P < .05) correlation (r = -.73 to r = -.55) between MCE defect size and normalized endocardial blood flow. Except at 15 minutes after reflow, there was poor correlation (r = .31 to r = .51) between MCE defect and infarct sizes. Even at 15 minutes after reflow, MCE defect size underestimated infarct size by 50%. In comparison, in the presence of dipyridamole, MCE defect size correlated strongly (r = .87, P < .001) with infarct size and reasonably well with normalized transmural blood flow (r = -.62, P = .04). Moreover, the topography of the MCE perfusion defect reflected the topography of the infarct. CONCLUSIONS: MCE revealed striking temporal heterogeneity in the spatial distribution of myocardial perfusion during postischemia reflow and either significantly underestimated or did not correlate with infarct size during reperfusion. Because of abnormalities in coronary vascular reserve specific to infarcted tissue, MCE in conjunction with intravenous dipyridamole depicted, in vivo, the actual topography of the infarct with remarkable accuracy.

Animals↗

Altered vascular responses to platelets from hypercholesterolemic humans.

Activated platelets release potent vasoactive factors. Previous studies have focused on mechanisms by which vascular abnormalities lead to altered responses of atherosclerotic arteries. We tested the hypothesis that the activation of platelets from hypercholesterolemic humans produces abnormal vascular responses. Responses to intraluminal and abluminal activation of platelets from normal subjects and type II hypercholesterolemic patients (total cholesterol, 274 +/- 16 [mean +/- SEM] mg/dl) were examined in carotid arteries from normal rabbits perfused in vitro. Intraluminal activation of normal platelets produced pronounced dilatation of arteries preconstricted with phenylephrine. Vasodilator responses to intraluminal activation of platelets from hypercholesterolemic patients were greatly impaired. Vasodilator responses to platelets from hypercholesterolemic patients were not restored to normal by LY53,857 (10(-5) M), a 5-hydroxytryptamine2-serotonergic antagonist, by SQ29,548 (10(-5) M), a thromboxane A2/prostaglandin H2 receptor antagonist, or by apyrase (1.5 units/ml), an enzyme with ADPase activity. Abluminal activation of normal platelets produced modest constriction in quiescent arteries, and abluminal activation of platelets from hypercholesterolemic patients produced augmented vasoconstrictor responses. The major finding is that vasodilator responses to platelets from hypercholesterolemic patients are profoundly impaired, and vasoconstrictor responses to platelets from hypercholesterolemic patients are augmented. Mechanisms in addition to increased release of serotonin, thromboxane, and ADP appear to contribute to impaired vasodilator responses to hypercholesterolemic platelets. Thus, alteration of platelets by hypercholesterolemia, as well as altered vascular reactivity, may contribute to abnormal vascular responses in atherosclerosis.

Adult↗

Two-dimensional echocardiographic assessment of regional left ventricular function and geometry following myocardial reperfusion.

Two-dimensional echocardiography is ideally suited for the serial noninvasive assessment of regional function and geometry following reperfusion therapy. Patients with substantial myocardial salvage show slow but definite recovery in regional function within the first 2 weeks. The extent of recovery seems to be associated with the degree of necrosis. Patients with some salvage, which is not enough to cause recovery in regional function, may demonstrate lack of infarct expansion and left ventricular (LV) dilatation. In the future, newer approaches such as pharmacologic challenge may play a role in defining post-ischemic myocardium early after the ischemic event.

Echocardiography↗

Quantifying myocardial blood flow with contrast echocardiography.

The principal focus of this article has been to discuss the issues relating to the quantitation of myocardial perfusion using MCE. In its current form, this technique can provide important physiological information in the cardiac catheterization laboratory and the operating room as well as in the experimental laboratory. Standardization of echo contrast agents, echo equipment, and algorithms for image analysis will make it a truly quantitative technique in the near future. MCE has the potential to offer the unique opportunity of simultaneously assessing regional myocardial flow and function in various ischemic syndromes.

Animals↗

Role of quantitative planar thallium-201 imaging for determining viability in patients with acute myocardial infarction and a totally occluded infarct-related artery.

We studied 57 patients with a recent infarction and an occluded infarct-related artery to test the hypothesis that the amount of 201Tl on delayed planar images correlates with the extent of viable myocardium after acute myocardial infarction. There was a significant (p < 0.001) correlation between mean 201Tl activity in the infarct zone and regional wall motion score in that zone both at baseline (r = -0.60, n = 57) and 1 mo after attempted angioplasty (r = -0.67, n = 48), with better function being associated with greater 201Tl uptake in the delayed images. There was no correlation between the number of segments showing redistribution and the wall motion score. We conclude that in patients with recent myocardial infarction and an occluded infarct-related artery, the average 201Tl activity within the infarct zone on delayed planar imaging correlates well with the extent of viable myocardium in that zone. The presence or absence of redistribution does not influence these results.

Adult↗

5'-Nucleotidase activity in retinol deficiency induced albino rats.

Retinol deficient rat liver, kidney and spleen showed a significant decrease in their enzyme activity (36% to 50%) compared to controls. The lectins could stimulate the enzyme activity in retinol deficient group by 57.6 to 92%, compared to controls (13.3% to 74%). Detergents increased the enzyme activity in retinol deficient tissue microsomes by 4.5%-80% in comparison to controls (10.3% to 119%). The results reveal alterations in membrane structure induced by retinol deficiency.

5'-Nucleotidase↗

An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction.

BACKGROUND: We hypothesized that successful reperfusion of an occluded infarct-related coronary artery even late after acute myocardial infarction would result in improved regional wall motion and that such improvement might be related to the presence of collateral blood flow within the infarct bed. METHODS: We assessed regional wall motion by two-dimensional echocardiography at base line and one month after angioplasty was attempted in the occluded infarct-related artery in 43 patients who had had a myocardial infarction two days to five weeks earlier. A wall-motion score was assigned to each patient on a five-point scale (from 1 [normal function] to 5 [dyskinesia]). The percentage of the infarct bed perfused by collateral flow was assessed with myocardial contrast echocardiography. RESULTS: In the 41 patients who had abnormal wall motion at base line, improvement in function was noted in 25 (78 percent) of the 32 in whom angioplasty was successful, as compared with only 1 (11 percent) of the 9 in whom it was unsuccessful (P < 0.001). The percentage of the infarct bed supplied by collateral flow at base line was directly correlated with wall function and inversely correlated with the wall-motion score one month after successful angioplasty (r = -0.64, P < 0.001). Among the patients in whom angioplasty was successful, the 23 in whom > 50 percent of the infarct bed was supplied by collateral flow had better wall motion (P < 0.001) and greater improvement in wall motion at one month (P = 0.004) than the 9 in whom < or = 50 percent of the bed was supplied by collateral flow. The degree of improvement in function was not influenced by the length of time between the infarction and the attempted angioplasty. CONCLUSIONS: The myocardium remains viable for a prolonged period in many patients with acute infarction and an occluded infarct-related artery. Viability appears to be associated with the presence of collateral blood flow within the infarct bed.

Angioplasty, Balloon↗

Clinical applications of myocardial contrast echocardiography.

Myocardial contrast echocardiography is a new technique that uses microbubbles of air in conjunction with simultaneously performed 2-dimensional echocardiographic imaging. Currently, it can be used to determine myocardial perfusion in the cardiac catheterization laboratory and the operating room. For myocardial contrast echocardiography to find a broader clinical application for the assessment of myocardial perfusion, it will be necessary to opacify the myocardium from venous injection of contrast in humans. In this regard, enhancement in bubble engineering, optimization of echocardiographic systems (greater sensitivity and dynamic range), and availability of digital image enhancement techniques will be required for myocardial contrast echocardiography to realize its full clinical potential by the year 2000.

Coronary Disease↗

High-performance liquid chromatographic determination of 2',3'-didehydro-3'-deoxythymidine, a new anti-human immunodeficiency virus agent, in human plasma and urine.

Sensitive and selective high-performance liquid chromatographic techniques have been developed for the determination of 2'-3'-didehydro-3'-deoxythymidine, d4T (BMY-27857), in human plasma and urine. The methods had linear standard curves over the concentration ranges 0.025-25.0 and 0.5-100 micrograms/ml for the plasma and urine matrices, respectively. Both methods used solid-phase extraction for isolating d4T and the internal standard, thymidine oxetane, from the biological matrix. In addition, the analytical column, mobile phase, instrumentation and chromatographic conditions used for both methods were identical. The ultraviolet absorbance of the column effluent was monitored at 266 nm. Results of analysis of quality control samples indicated that the intra-assay precision values, as measured by percent relative standard deviation, were within 12 and 3%, and accuracy samples deviated less than 10 and 5% from nominal values for the plasma and urine assays, respectively.

Adult↗

Value and limitations of current methods of evaluating patients presenting to the emergency room with cardiac-related symptoms for determining long-term prognosis.

The goal of this study was to determine the value and limitations of the current approach for evaluating patients in the emergency room (ER) with cardiac-related symptoms in terms of predicting long-term outcome. Accordingly, 274 consecutive prospectively identified patients presenting to the ER with such symptoms were evaluated, and follow-up was obtained at 20 +/- 9 months in 265 of them (97%). Adverse cardiovascular events were defined as: nonfatal myocardial infarction, death, cerebrovascular accident with neurologic deficit, life-threatening arrhythmia and cardiac surgery. Eighty-three patients (31%) had a cardiovascular event during follow-up; 42 occurred within 48 hours of ER presentation, whereas 41 occurred in the ensuing months. Findings on physical examination and electrocardiogram provided additional prognostic information, compared with that of history alone, when added sequentially into a Cox model. However, by discriminant function analysis, only 63% of actual events were correctly predicted by the model. Events occurring after 48 hours of ER presentation were correctly predicted only 50% of the time compared with those occurring within 48 hours of ER presentation, which were correctly predicted 75% of the time (p = 0.04). It is concluded that patients presenting to the ER with cardiac-related symptoms are at high risk for adverse cardiovascular events. The likelihood of an event occurring after 48 hours of presentation is as high as one occurring within 48 hours. Current methods of evaluating such patients have limited prognostic value, particularly for those at long-term risk for events.

Aged↗

Meningococcal disease in Wales: clinical features, outcome and public health management.

In Wales, in 1988, 119 patients with meningococcal disease were identified, so giving a crude annual incidence of 4.2 patients per 100,000 population. The combined classical clinical features of fever, vomiting, neck stiffness, headache and purpuric rash were identified in only 9% of patients. Fever and vomiting were the commonest symptoms, both being present in 60% of patients. A rash was noted in 77% of patients but neck stiffness in only 39%. Rash was more common in children, headache and photophobia in adults. A total of 13 patients died, the fatality rare increasing with age from 3% in infants to 20% in older teenagers and adults. Only 15% of 75 patients admitted to hospital by general practitioners were known to have received intravenous or intramuscular penicillin before admission as recommended by the Chief Medical Officers of the Health Departments in the U.K. Only 24% of patients received rifampicin to clear nasopharyngeal carriage before or at discharge from hospital. Altogether, 375 household contacts of patients were identified. At least 84% of them received chemoprophylaxis.

Acute Disease↗

Comparison of immune responses to a native viral antigen and a synthetic peptide derived from it: implications for vaccine development.

Murine immune responses to the hepatitis B surface antigen (HBsAg) and a synthetic peptide derived from it were compared at the humoral level. Six of nine strains used responded to either peptide or HBsAg, though restriction profiles were not superimposable. Two of three strains non-responsive to HBsAg produced an antibody response on immunization with peptide which was cross-reactive with both peptide and HBsAg. In in vitro lymphocyte stimulation assays, lymphocyte from all six peptide-immunized mouse strains could be induced to proliferate on challenge with HBsAg. However, of the HBsAg-immunized groups, lymphocytes from only three of six responder strains proliferated on in vitro HBsAg challenge. Cumulatively, these results suggest that a vaccine formulation that includes both protein antigens and synthetic peptides derived from these proteins may be more effective at eliciting an immune response in a broader cross-section of target population.

Animals↗