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Biomedical subjects

C Eng

Publications and source records attributed to C Eng.

At least 253 records · Page 14Linked to original sources

Improvement of coronary blood flow by augmentation of coronary vascular compliance.

Coronary blood flow occurs predominantly during the diastolic period of the cardiac cycle. This study investigated the effects of increasing the diastolic coronary perfusion pressure by artificially increasing the epicardial coronary capacitance function, using a buffer chamber. The left anterior descending (LAD) coronary artery was cannulated in six dogs and perfused by tubing via the carotid artery. A significant stenosis was produced with a screw clamp, resulting in a distal coronary pressure of about 35 mm Hg. A buffer chamber was placed on the perfusion line distal to the stenosis to buffer the distal coronary perfusion pressure. Myocardial blood flow as measured by microspheres showed a 39.6% increase in blood flow during buffered perfusion as compared to nonbuffered perfusion: 0.415 +/- 0.279 versus 0.316 +/- 0.238 ml/min/g. The calculated diastolic pressure time index (DPTI) increased 54.1% during buffered perfusion. Flow increased significantly in the endocardial and mid-wall layers but not in the epicardium. It is concluded that coronary blood flow can be augmented by increasing the coronary capacitance function in this model.

Animals↗

Effects of vasopressin on the coronary circulation: reserve and regulation during ischemia.

In 18 dogs, intracoronary infusion of vasopressin produced a 40% reduction in coronary flow without significantly affecting systemic hemodynamics. The blood flow reduction occurred in a uniform transmural pattern without evidence of a gradient. The reduction in coronary flow resulted in a decrease in regional contractility as determined by isometric strain gauge arches. The decrease in regional contractility was transiently reversed by bolus injection of adenosine into the perfusion line. This suggests that the reduction of blood flow due to vasopressin was causing ischemia. Evidence for ischemia was also supported by measurements of local vein and tissue lactate production. Despite the apparently ischemic conditions, the vascular bed demonstrated evidence for significant reserve and regulation. Pressure-flow relationships performed under control and during vasopressin infusion demonstrated that the coronary vasculature retained its ability to regulate or defend a given level of coronary flow over a range of coronary perfusion pressures. Vasopressin produced a mild decrease in the peak hyperemic flow after a 15-s coronary occlusion and shortened the duration of reactive hyperemia. These overall findings are compatible with a predominant vasoconstrictor effect on the distal coronary vasculature. A role for a myogenic factor in the control of the coronary circulation is suggested, which is amplified by vasopressin.

Animals↗

Complete transformation by adenovirus 2 requires both E1A proteins.

Rodent cells transformed by adenovirus 2 (Ad2) express two highly related viral proteins of 289 and 243 amino acids encoded in early region 1A (E1A). Transformation studies were performed with adenovirus mutants that express only one or the other E1A protein. We found that the 289 amino acid protein, which has transcription inducing activity, and the 243 amino acid protein, which has little if any of this activity, were both required to produce the fully transformed phenotype. Expression of either E1A protein induced a partially transformed phenotype. The 243 amino acid protein was particularly important for anchorage independent growth. As found in previous studies with several other E1A mutants, the process of transformation by the mutant that expresses the 243 amino acid protein only was cold-sensitive. While the 289 amino acid protein is the only E1A protein required for efficient viral replication under standard cell culture conditions, the 243 amino acid protein in addition to the 289 amino acid protein was found to be required for efficient viral replication in growth-arrested human cells.

Adenoviruses, Human↗

Bayesian comparison of cost-effectiveness of different clinical approaches to diagnose coronary artery disease.

The objective of this study was to compare the cost-effectiveness of four clinical policies (policies I to IV) in the diagnosis of the presence or absence of coronary artery disease. A model based on Bayes' theorem and published clinical data was constructed to make these comparisons. Effectiveness was defined as either the number of patients with coronary disease diagnosed or as the number of quality-adjusted life years extended by therapy after the diagnosis of coronary disease. The following conclusions arise strictly from analysis of the model and may not necessarily be applicable to all situations. As prevalence of coronary disease in the population increased, it caused a linear increase in cost per patient tested, but a hyperbolic decrease in cost per effect, that is, increased cost-effectiveness. Thus, cost-effectiveness of all policies (I to IV) was poor in populations with a prevalence of disease below 10%, for example, asymptomatic people with no risk factors. Analysis of the model also indicates that at prevalences less than 80%, exercise thallium scintigraphy alone as a first test (policy II) is a more cost-effective initial test than is exercise electrocardiography alone as a first test (policy I) or exercise electrocardiography first combined with thallium imaging as a second test (policy IV). Exercise electrocardiography before thallium imaging (policy IV) is more cost-effective than exercise electrocardiography alone (policy I) at prevalences less than 80%. 4) Noninvasive exercise testing before angiography (policies I, II and IV) is more cost-effective than using coronary angiography as the first and only test (policy III) at prevalences less than 80%. 5) Above a threshold value of prevalence of 80% (for example patients with typical angina), proceeding to angiography as the first test (policy III) was more cost-effective than initial noninvasive exercise tests (policies I, II and IV). One advantage of this quantitative model is that it estimates a threshold value of prevalence (80%) at which the rank order of policies changes. The model also allows substitution of different values for any variable as a way of accounting for the uncertainty inherent in the data. In conclusion, it is essential to consider the prevalence of disease when selecting the most cost-effective clinical approach to making a diagnosis.

Angiography↗

Myocardial micronecrosis produced by microsphere embolization. Role of an alpha-adrenergic tonic influence on the coronary microcirculation.

Microspheres approximately 25 or 50 micrometers in diameter were systemically embolized from the left ventricular cavity. The number of microspheres given was empirically chosen to minimize the possibility of more than one microsphere lodging in an arteriole (3 mg/kg), yet was sufficient to allow for adequate histological assessment. The dogs were sacrificed after 24 hours, and focal areas of myocytolytic necrosis were noted in the myocardium. Groups of dogs were given pretreatment with drugs 10 minutes before embolization. Dogs pretreated with phentolamine (n = 8) and prazosin (n = 2) did not reveal any areas of myocardial necrosis after embolization with 25-micrometers microspheres. Cardiac lesions were also prevented in four of five dogs pretreated with verapamil. In contrast, cardiac lesions were not prevented by pretreatment with yohimbine (n = 2), dipyridamole (n = 3), propranolol (n = 2), or atropine (n = 2). Drug pretreatment with phentolamine or verapamil was not able to prevent cardiac lesions after embolization with 50-micrometers microspheres. Furthermore, despite a greater number of microspheres physically present in the subendocardial layer, the necrotic lesions were more frequent in the mid-wall and epicardial layers. Lesions produced by 25- or 50-micrometers emboli were also significantly smaller in the endocardium. Systemic embolization with microspheres excluding the coronary circulation did not produce cardiac lesions. We conclude that mechanical interruption of the coronary circulation with a 25-micrometers microsphere may be a necessary but not sufficient condition to produce cardiac necrosis. An alpha 1-adrenergic mechanism is also involved in the production of these lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Flow into ischemic myocardium and across coronary collateral vessels is modulated by a waterfall mechanism.

If a coronary artery is ligated and the distal end cannulated, blood flows retrograde from the cannula when vented to the atmosphere. By varying the height of the outflow tubing, and thereby changing the outflow pressure, pressure-flow relationships can be constructed. We used this technique in eight dogs to assess the characteristics of blood flow into ischemic myocardium. Above a back pressure of 10 mm Hg, increasing back pressure resulted in a decrease of retrograde blood flow. However, below a back pressure of about 10 mm Hg (10.7 +/- 2.7 mm Hg), alterations in back pressure did not result in changes in retrograde blood flow (back pressure-independent region). The transition at 10 mm Hg is interpreted as the critical waterfall pressure in ischemic myocardium. In another group of eight dogs, the ischemic bed was completely embolized with 25-micron sized microspheres to prevent RBF from entering the tissue as back pressure was raised. Pressure-flow relationships performed in this group revealed a back pressure-independent region that extended to approximately 20 mm Hg (23.0 +/- 2.5 mm Hg). This behavior of the pressure-flow relationship is consistent with a waterfall phenomenon on the collateral vessels. To the extent that collateral vessels in the dog are mainly epicardial in location, the findings suggest that extravascular pressures of 20 mm Hg can occur in the more superficial layers of the heart. In addition, the waterfall on the collaterals indicates that this mechanism can operate on nonvenous vessels. Our results suggest separate waterfall phenomena operating on the collateral vessels (20 mm Hg) and on the vessels in the ischemic myocardium (10 mm Hg).

Animals↗

Chenodeoxycholic acid-3-sulfate. Metabolism and excretion in the rat and hamster and effects on hepatic transport systems.

The metabolism and excretion of chenodeoxycholic acid-3-sulfate were determined in rats and hamsters. Constant intravenous infusions of 1, 2, and 3 mumoles/min in rats gave a maximum excretion in bile of 1.25 mumoles/min. Simultaneous infusions of sodium taurocholate at 2.0 mumoles/min and sulfobromophthalein at 0.2 mumole/min had no effects on the maximum excretion rate of chenodeoxycholic acid-3-sulfate. However, the bile acid ester sulfate caused a dose-related reduction in the excretion rate of BSP without affecting bile acid excretion rate and without a reduction in total bile flow. Chromatographic analysis of ester sulfate, a bile acid recovered in bile and urine, indicated that more than 95% had not undergone further metabolic transformation.

Animals↗

Can noninvasive exercise test criteria identify patients with left main or 3-vessel coronary disease after a first myocardial infarction?

This study attempts to determine whether exercise treadmill testing with clinical, electrocardiographic, and thallium-201 myocardial perfusion imaging data can identify which patients have left main or 3-vessel (anatomically high-risk) coronary artery disease (CAD) after their first transmural myocardial infarct (MI). Twelve exercise test criteria for high-risk disease were compared in 40 patients referred for cardiac catheterization; 34 had a history of chest pain and 17 had angiographically defined high-risk CAD. A thallium image defect outside the vascular distribution of the MI was the most reliable criterion to distinguish patients with high-risk CAD (p = 0.00052 for Fisher's exact test of discrimination). Thallium imaging was somewhat more sensitive (92 versus 65%, p = 0.108) when patients with negative thallium imaging criteria who failed to achieve 85% of the age-predicted maximal heart rate were excluded. Failure to achieve 85% of predicted heart rate was by itself a useful criterion for detecting high-risk CAD (p = 0.017), especially in patients not taking propranolol (p = 0.004). Development of positive S-T segment depression at less than 70% predicted heart rate also discriminated left main or 3-vessel disease from less extensive CAD (p = 0.016). Other criteria failed to discriminate significantly between high-risk and less extensive CAD in patients after their first MI (p greater than 0.05). S-T segment depression (p = 0.199) or chest pain (p = 0.577) during exercise testing were particularly unreliable. Further, none of the criteria for high-risk CAD were influenced by irreversible left ventricular dysfunction. It is concluded that patients with thallium imaging defects outside the region of the infarct, decreasing blood pressure during exercise, failure to achieve 85% of predicted heart rate, or S-T depression at less than 70% of predicted heart rate have a high probability of having left main or 3-vessel disease. Patients without these criteria have a very low probability of having high-risk CAD and probably do not need coronary angiography for the purpose of excluding these high-risk coronary lesions after a first MI.

Adult↗

Comparative effect of verapamil and nitroglycerin on collateral blood flow.

The effects of intracoronary verapamil and nitroglycerin on collateral blood flow were compared under conditions where coronary perfusion pressure was held constant with a servopump and the systemic effects of the drugs were minimal. Both drugs were infused into 12 anesthetized dogs after occlusion of the left anterior descending coronary artery (LAD) and regional myocardial blood flow (MBF) was measured using microspheres. Before the LAD occlusion, the myocardium not perfused by the LAD was labeled to permit calculation of the fraction of tissue normally perfused in the LAD samples and corrections for collateral flow. The central ischemic zone contained 2.5 +/- 0.3% normally perfused myocardium and a 4-mm border zone contained 26.8 +/- 4.3% normal myocardium. This border zone contained 10% of the total tissue supplied by the LAD. The MBF in the central ischemic zone increased from 0.101 +/- 0.019 to 0.113 +/- 0.022 ml/min/g after verapamil infusion (NS) and to 0.149 +/- 0.024 ml/min/g after nitroglycerin (p less than 0.01). Uncorrected MBF in the border zone increased significantly after infusion of both verapamil (0.469 +/- 0.085 ml/min/g, p less than 0.01) and nitroglycerin (0.398 +/- 0.056, p less than 0.05). When corrections were made for interdigitating normal tissue in the border zone, only the MBF after nitroglycerin was significantly increased. Thus, nitroglycerin significantly increased the collateral blood flow to ischemic tissue in the central ischemic and border zones, but verapamil did not.

Animals↗

Physiological influences on perfusion imaging in transient myocardial ischaemia: importance of early distribution of thallium-201.

We tested the hypothesis that visualisation of defects on thallium-201 (201Tl) myocardial perfusion images (MPI) depends on the duration of the ischaemic state between 201Tl injection and the time of reperfusion of an occluded coronary artery. Praecordial imaging with a gamma camera was performed in 24 anaesthetised, open-chest dogs with transient coronary occlusion. Results indicated that if the duration of the ischaemic state after 201Tl injection was less than 3 min before reperfusion, then the MPI 5 to 15 min after 201Tl injection was falsely negative (201Tl activity in zone (IZ)/normal zone (NZ)greater than 0.85). Dogs which were ischaemic more than 5 min always had MPI defects 5 to 15 min after 201Tl injection (IZ/NZ201Tl ratio less than 0.85). MPI results (201Tl IZ/NZ) 15 min after 201Tl injection were determined by the duration of the ischaemic state after 201Tl injection (r = -0.86) because prolonged ischaemia allowed 201Tl to distribute from blood to myocardium before reperfusion: 201Tl (IZ/NZ( = 0.356 +/- 1.00 (fraction of total 201Tl remaining in blood at the end of the ischaemic state), r = 0.94.

Animals↗

Coronary collateral function during exercise.

A totally occluded coronary vessel subtending a noninfarcted, entirely collateral-dependent myocardial region (NIECDMR) provides an opportunity to assess collateral perfusion during exercise stress. Collateral function was determined by analysis of exercise thallium-201 myocardial perfusion images from 31 patients who had at least one NIECDMR (total 41 NIECDMRs) documented during catheterization. Twenty-two of 41 NIECDMRs manifested exercise-induced perfusion defects and 19 were normally perfused. The exercise-negative NIECDMRs were further categorized: Group 1 NIECDMRs (n = 13) were associated with defects in other myocardial regions supplied by diseased vessels and were considered negative relative to other jeopardized regions; group 2 NIECDMRs (n = 6) were not associated with exercise-induced defects in other myocardial regions, which suggests that collateral perfusion was adequate during maximal exercise. Regions supplied by a diseased left anterior descending coronary artery manifested exercise defects regardless of collaterals, possibly because these regions were larger and required more perfusion. Angiographic indexes of collateral function did not clearly predict exercise results.

Adult↗

The effects of the coronary capacitance on the interpretation of diastolic pressure-flow relationships.

The effects of coronary capacitance on instantaneous pressure-flow (P/F) relationships were analyzed using a theoretical model of coronary flow during diastole that included capacitance. The magnitude of the discrepancy between actual intramural and instantaneously derived P/F relationships was predicted to be dependent on the ratio of two natural decay constants (central aortic decay constant/intrinsic coronary decay constant). The effects of coronary capacitance are eliminated using constant pressure conditions. The instantaneous (dynamic) and constant pressure (static) P/F relationships were compared experimentally using a reservoir to provide constant pressure perfusion during prolonged diastoles in heart blocked dogs. In the presence of coronary tone, zero flow pressure intercepts (Pzf) of 27.1 +/- 6.6 and 11.0 +/- 3.0 mm Hg were obtained under dynamic and constant pressure conditions respectively, P less than 0.001. After maximal vasodilation, Pzf of 14.2 +/- 4.5 mmHg and 10.7 +/- 2.4 mmHg were obtained under dynamic and constant pressure conditions, respectively, P = NS. Pzf derived under constant pressure conditions were independent of the state of coronary vasomotor tone with a value about 11 mmHg. The slopes of the dynamic P/F relationships tended to be greater than those derived from constant pressure conditions. This may suggest an additional component of increasing coronary resistance during diastole that could not be readily assessed under dynamic conditions. We conclude that coronary capacitive effects and resistance changes during diastole severely limit the interpretation of instantaneous dynamic P/F relationships. Diastolic coronary perfusion ceases at about 11 mm Hg and is independent of coronary tone when capacitive effects are eliminated.

Animals↗

Breath concentration as an index of the health risk from benzene. Studies on the accumulation and clearance of inhaled benzene.

Human subjects were exposed to known concentrations of benzene in air for single and repeated daily periods. The breath concentrations measured repeated exposures approached a maximum after 3 d, and this phenomenon indicated that the tissues were approaching saturation under the experimental conditions. The breath concentrations measured after exposure indicated an initial rapid clearance of benzene with a half-time of 2.6 h, followed by a slower phase with a half-time of 24 h. The decay in breath concentration after prolonged occupational exposure appeared to be slower; the difference between the laboratory and industrial studies was, however, not significant. The hygienic significance of these results was discussed, and it was recommended that control measures be employed when a morning breath concentration exceeds 10 ppb.

Atmosphere Exposure Chambers↗