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Biomedical subjects

C Eng

Publications and source records attributed to C Eng.

At least 271 records · Page 15Linked to original sources
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1980

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↗
PubMed1976

Serum quinidine levels after chronic administration of four different quinidine formulations.

The serum levels produced by four different quinidine formulations have been studied. The relative bioavailability of the formulations was demonstrated as were the mean peak serum levels and their timing in relation to dosage. From the data obtained, the biological half-lives were measured and the apparent volume of distribution and total body clearance were calculated for each formulation. The generic tablets of quinidine monosulphate from five different manufacturers were not significantly different from each other in any respect and produced the expected peak and trough serum level curves. The serum level curves resulting from administration of quinidine polygalacturonate (Cardioquin) were not significantly different from those resulting from the generic tablets, and this formulation may be regarded as therapeutically equivalent to the generic formulations. Both sustained-release formulations of quinidine bisulphate, Durettes and Kiditard (given at the same dosage) were shown to offer a means whereby, with simple twice-daily dosage, quinidine maintenance treatment may be continued with the confidence that the serum levels may be maintained throughout each 24-hour period without peaks into the toxic levels and troughs into the levels of no effect.

Adult↗
PubMedDate not supplied

The effect of coronary arterial pressure on myocardial distensibility. Absence of a "garden hose" effect during in-vivo conditions.

The effect of the coronary perfusion pressure on myocardial distensibility was studied in 11 open-chest dogs. The left anterior descending coronary artery was cannulated, and coronary perfusion pressure and blood flow were measured. Regional myocardial segment length was measured using sonomicrometers. The temporal relationship between the phasic coronary pressure fall and change in myocardial segment length was analyzed during the early phase of coronary occlusion. Diastolic myocardial segment length was completely unaffected by the substantial fall in coronary pressure over a period of 9.3 +/- 0.8 s (20 +/- 2 heart beats). During this period, coronary pressure fell from 98 +/- 7 to 28 +/- 2 mm Hg. Subsequently, diastolic segment length increased, presumably due to ischemia rather than to a delayed compliance change. In order to differentiate between a possible long-time constant for coupling of the intravascular pressure to myocardial compliance versus a primary ischemic effect, regional cardiac contraction was abolished by an intracoronary potassium chloride infusion in three dogs. Coronary occlusion during regional cardioplegia produced no further segment length changes for a 1-min period, effectively excluding viscoelastic coupling time constants of up to 1 min. From these results we conclude that the coronary distending pressure does not contribute to passive myocardial properties over the physiological perfusion pressure range, and that the "garden hose" effect is not operative for the in vivo working heart.

Animals↗
PubMedDate not supplied

Rapid mutation scanning of genes associated with familial cancer syndromes using denaturing high-performance liquid chromatography.

Germline mutations in tumor suppressor genes, or less frequently oncogenes, have been identified in up to 19 familial cancer syndromes including Li-Fraumeni syndrome, familial paraganglioma, familial adenomatous polyposis coli and breast and ovarian cancers. Multiple genes have been associated with some syndromes as approximately 26 genes have been linked to the development of these familial cancers. With this increased knowledge of the molecular determinants of familial cancer comes an equal expectation for efficient genetic screening programs. We have trialled denaturing high-performance liquid chromatography (dHPLC) as a tool for rapid germline mutation scanning of genes implicated in three familial cancer syndromes -- Cowden syndrome (PTEN mutation), multiple endocrine neoplasia type 2 (RET mutation) and von Hippel-Lindau disease (VHL mutation). Thirty-two mutations, including 21 in PTEN, 9 in RET plus a polymorphism, and 2 in VHL, were analyzed using the WAVE DNA fragment analysis system with 100% detection efficiency. In the case of the tumor suppressor gene PTEN, mutations were scattered along most of the gene. However, mutations in the RET proto-oncogene associated with multiple endocrine neoplasia type 2 were limited to specific clusters or "hot spots." The use of GC-clamped primers to scan for mutations scattered along PTEN exons was shown to greatly enhance the sensitivity of detection of mutant hetero- and homoduplex peaks at a single denaturation temperature compared to fragments generated using non--GC-clamped primers. Thus, when scanning tumor suppressor genes for germline mutation using dHPLC, the incorporation of appropriate GC-clamped primers will likely increase the efficiency of mutation detection.

Chromatography, High Pressure Liquid↗