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Biomedical subjects

L Roy

Publications and source records attributed to L Roy.

At least 91 records · Page 5Linked to original sources
PubMed1986

Platelet activation in unstable coronary disease.

Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Biosynthesis of thromboxane in patients with systemic sclerosis and Raynaud's phenomenon.

Thromboxane A2, the predominant cyclo-oxygenase product of arachidonic acid in platelets, is a potent vasoconstrictor and platelet agonist. Analysis of urinary metabolites by gas chromatography and mass spectrometry is a specific non-invasive method of measuring the biosynthesis of thromboxane that avoids the problem of platelet activation ex vivo. Excretion of the major urinary thromboxane metabolite, 2,3-dinor-thromboxane B2, was significantly increased (p less than 0.001) in 10 patients (nine women) with systemic sclerosis complicated by Raynaud's phenomenon compared with healthy controls (486 (SD 88) v 162 (38) ng/g creatinine) and increased further in the patients (to 1007 (212) ng/g creatinine) during application of a cold stimulus sufficient to induce digital vasoconstriction. Consistent with an increase in platelet-vascular interactions in vivo, excretion of a prostacyclin metabolite was also significantly increased (p less than 0.005) in the patients with systemic sclerosis (248 (39) v 112 (10) ng/g creatinine) and tended to increase further on cooling. Biosynthesis of thromboxane is increased in patients with systemic sclerosis and may exacerbate digital vasospasm that such patients develop when cold. This observation and the concomitant increase in the formation of prostacyclin provide a rationale for evaluating compounds that prevent the synthesis of thromboxane A2 or inhibit its action while preserving the potential homoeostatic role of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Adiaspiromycosis in striped skunks in Alberta, Canada.

Pulmonary adiaspiromycosis was diagnosed in seven of 25 striped skunks (Mephitis mephitis) in east-central Alberta. The infection varied from mild, where only microscopic lesions were seen, to severe, where gross lesions of grayish-white nodules were observed in the lung parenchyma. Mild lesions were restricted to the lung, while severe lesions extended to the tracheobronchial and mediastinal lymph nodes. Histologically, the lesions were characterized by a centrally located fungal spherule, surrounded by granulomatous inflammation. The morphology of the fungal spherules was consistent with that of Emmonsia crescens. By electron microscopy, the fungal cells had an outer thick fibrillar wall and an inner cytoplasm filled with large lipid vacuoles with relatively few mitochondria, ribosomes or glycogen inclusions. The absence of endosporulation and budding suggested that each fungal cell in the lung represented a separate inhaled spore. Infection was by inhalation, nevertheless adiaspores may disseminate to the regional lymph nodes.

Animals↗
PubMed1985

Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease.

The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.

Adult↗
PubMed1985

Lack of efficacy of nafazatrom, a novel anti-thrombotic compound, in patients with coronary artery disease.

Nafazatrom (Bay G 6575) is a novel antithrombotic compound, which acts by stimulation of prostacyclin as well as by inhibition of lipoxygenase enzymes. To determine its effects on exercise performance in coronary artery disease patients, a double-blind study was conducted. Twenty patients with coronary artery disease underwent an exercise stress test before and 2 hours after administration of placebo or nafazatrom (1.2 gm). Before the drug administration, there was evidence of enhanced platelet activity, as reflected by elevated resting plasma beta thromboglobulin and thromboxane B2 concentrations. Plasma 6-keto-PGF1 alpha levels were undetectable in most patients. All coagulation tests were in the normal range. None of these parameters changed with exercise. Administration of placebo or nafazatrom before the exercise stress test did not significantly influence any of the coagulation or platelet function parameters or plasma concentrations of thromboxane B2 and 6-keto-PGF1 alpha. This lack of effect was evident both at rest and upon exercise. Compared to placebo, nafazatrom did not significantly increase exercise tolerance time or exercise-induced symptoms. In conclusion, nafazatrom did not influence exercise performance in patients with coronary disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Endogenous biosynthesis of prostacyclin during cardiac catheterization and angiography in man.

The potent platelet inhibitory and vasodilator properties of prostacyclin suggest that levels of this substance may be of relevance to drug action and pathologic processes in the coronary vascular bed. Attempts to estimate the coronary secretion rate of prostacyclin have relied on measurements of metabolites obtained via cardiac catheter, usually as an adjunct to coronary angiography. To test the hypothesis that such procedures might themselves perturb endogenous biosynthesis of prostacyclin we used mass spectrometry to measure plasma levels of 6-keto-prostaglandin (PG) F1 alpha across the coronary vascular bed, as well as to assess the excretion of a major urinary metabolite, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), in patients undergoing cardiac catheterization. PGI-M excretion increased variably from a median 100 to 205 pg/mg creatinine (p less than .01) during catheterization with angiography and remained elevated 2 to 4 hr after initiation of the procedure. However, cardiac catheterization without angiography also stimulated metabolite excretion, perhaps reflecting catheter-induced vascular trauma. The direct effect of radiocontrast media on vascular release of prostacyclin was indicated by increased PGI-M excretion in healthy volunteers administered intravenous radiocontrast and by studies of the canine coronary artery and jugular vein in vitro. Measurement of plasma 6-keto-PGF1 alpha after left heart catheterization showed that levels in aortic (21 +/- 8 pg/ml) and coronary sinus (14 +/- 2 pg/ml) blood were increased compared with peripheral venous levels (less than or equal to 4 + 1 pg/ml) determined before this procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

[Non unionized professional pilots in Québec : from myth to real.].

In this article, the working conditions of 875 non syndicated professional pilots who work on small third class airline companies are analysed. This research was made on behalf of the pilots themselves through the intermediary of the Association of the Air People of Quebec. First, a socio-demographic profile of this masculine man power is outlined, made of young and low income persons. Emphasis is put on the working characteristics that are risk factors for health and security and on sources of stress for the pilots which are: the seasonal peaks, recurrent unemployment, remuneration by the volume of work done, un-sufficient rest, the employer's threats, the deficient state of the airplanes. It is also shown that certain symptoms are present in these workers: a general fatigue, headaches and insomnia. Lastly, their perception of their work and the satisfaction gained from it is presented.

English Abstract↗
PubMed1984

The effects of organic nitrates on prostacyclin biosynthesis and platelet function in humans.

The results of prior studies indicate that nitroglycerin stimulates prostacyclin release by cultured endothelium and by the coronary vasculature in vivo. However, the accuracy of these findings in coronary vasculature relies on plasma samples obtained from the circulation via cardiac catheters, a procedure we have shown to stimulate prostacyclin release, thereby confounding interpretation of drug action. We studied the effects of short-acting (nitroglycerin) and long-acting (isosorbide dinitrate) nitrates on a noninvasive index of prostacyclin synthesis, excretion of urinary 2,3-dinor-6-keto-PGF1 alpha. Nitroglycerin was infused into six subjects to either a maximum of 480 micrograms/min or until mean arterial pressure fell by 20 mm Hg. Urine was collected for negative ion chemical ionization gas chromatographic, mass spectrometric analysis before and during the nitroglycerin infusion and for two 2 hr periods after nitroglycerin. The peak nitroglycerin infusion rate was 387 +/- 67 micrograms/min, which caused a fall in supine blood pressure (systolic/diastolic) of 11 +/- 5/14 +/- 4 mm Hg and a 12 +/- 3 beats/min increase in heart rate. Excretion of 2,3-dinor-6-keto-PGF1 alpha (pg/mg creatinine) was unchanged from control infusion values (106 +/- 19.5) either during (123 +/- 21) or after (134 +/- 14.6; 139 +/- 36) nitroglycerin infusion. Platelet aggregation to arachidonic acid (0.33 to 1.33 microM) and epinephrine (1 to 10 microM) ex vivo was inhibited in only one subject in whom excretion of 2,3-dinor-6-keto-PGF1 alpha was unaltered. Serum thromboxane B2 was not changed by nitroglycerin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Biochemical and ultrastructural integrity of the saphenous vein conduit during coronary artery bypass grafting. Preliminary results of the effect of papaverine.

Factors associated with early and late graft patency related to aorta-coronary artery bypass grafting with a reversed segment of saphenous vein are clinically important. The present investigation examines the biochemical and electron microscopic integrity of this venous conduit intraoperatively with regard to pharmacologic manipulation with papaverine. Portions of saphenous vein were analyzed in 22 patients undergoing coronary artery bypass operations. Levels of a stable derivative of prostacyclin, 6-keto-PGF1 alpha, were measured by radioimmunoassay. Scanning as well as transmission electron microscopy was also performed. In particular, the efficacy of local vein treatment with papaverine, a phosphodiesterase inhibitor, was evaluated. We found that levels of 6-keto-PGF1 alpha in venous effluent showed a biphasic response with initial elevation followed by a relative depression after papaverine exposure. There were no such changes observed in veins subjected to a balanced electrolyte solution (Plasma-Lyte). In addition, levels of the platelet-inhibitory substance 6-keto-PGF1 alpha in venous tissue were less in papaverine-treated veins than those found in veins treated only with the balanced electrolyte solution (Plasma-Lyte). Furthermore, evidence for ultrastructural damage was also somewhat greater in the papaverine-treated group. An alternative method of dilating the saphenous vein after harvesting, which involves the creation of the proximal aorta-coronary anastomosis first and gentle finger manipulation subsequently, appeared to minimize venous injury. Under present clinical conditions, it appears that some amount of injury is inevitable during harvesting and suturing of the human saphenous vein during coronary bypass grafting.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Increased plasma concentrations of prostacyclin metabolite 6-keto-PGF1 alpha in essential hypertension. Influence of therapy with labetalol.

To evaluate the role of the vasoactive prostaglandins prostacyclin and thromboxane A2 in essential hypertension, the stable metabolites 6-keto-PGF1 alpha and thromboxane B2, respectively, were measured in plasma before and after therapy in 7 patients. During the placebo phase, plasma 6-keto-PGF1 alpha levels were significantly greater than normal. Plasma thromboxane B2 levels were not statistically different from those in normal subjects. After intravenous administration of labetalol to the point of blood pressure reduction, neither plasma 6-keto-PGF1 alpha nor thromboxane B2 values changed. With prolonged oral labetalol therapy and concurrent regulation of blood pressure, a significant decrease in plasma 6-keto-PGF1 alpha levels occurred while thromboxane B2 values remained unaltered. Elevation of plasma 6-keto-PGF1 alpha in untreated hypertensive subjects suggests that enhanced vessel wall prostacyclin synthesis may be a protective mechanism to prevent organ damage. As blood pressure is controlled this increase is no longer needed, and prostacyclin generation returns to normal.

Administration, Oral↗
PubMed1983

Coronary vasodilator reserve impairment distal to systolic coronary artery compression in dogs.

To investigate the mechanism by which muscular coronary overbridging can cause myocardial ischaemia, we studied the effect of systolic compression (SC) of the proximal left circumflex coronary artery in ten anaesthetised dogs, with both intact autoregulation and maximally dilated coronary arteries. Systolic compression was produced by a mechanical device adjusted to interrupt circumflex coronary flow only during the aortic ejection period and we measured left ventricular, aortic and distal circumflex coronary pressures, phasic coronary blood flow, regional myocardial blood flow (RMBF), myocardial oxygen consumption (MVO2), and myocardial lactate extraction (MLE). During both autoregulation and maximal coronary vasodilatation, there was a diastolic time lag after SC to restart phasic circumflex coronary blood flow (34 +/- 3 vs 31 +/- 3 ms) and to increase distal circumflex coronary pressure (69 +/- 4 vs 79 +/- 6 ms). With autoregulation, SC reduced the diastolic circumflex coronary: systolic left ventricular pressure time ratio (DPTIc:SPTI) and there were no changes in the other measured variables. During maximal coronary vasodilatation and SC, the coronary vasodilator reserve, the DPTIc:SPTI ratio and the inner:outer myocardial blood flow distribution were decreased in the territory of the left circumflex coronary artery; a linear relationship was observed between the DPTIc:SPTI and the inner:outer myocardial blood flow ratio. Systolic compression during vasodilatation also produced a reduction in myocardial oxygen consumption of the whole heart and a production of lactate in the coronary sinus. These results suggest that myocardial ischaemia with a myocardial bridge is due to the combined effects of a diastolic time lag to repressurise the coronary vascular bed, of tachycardia and of coronary vasodilatation.

Animals↗
PubMed1982

Comparison of umbilical vein models for measurement of relative prostacyclin and thromboxane production.

There is growing evidence that blood vessels generate TXA2 in addition to PGI2. We examined effluents from continuously perfused human umbilical vein and supernatants from umbilical vein rings for TXB2 and 6-keto-PGF1 alpha measurements (stable metabolites of TXA2 and PGI2, respectively). TXB2 and 6-keto-PGF1 alpha were identified in all samples. 6-keto-PGF1 alpha to TXB2 ratio was higher in intact vein effluents than in the venous ring supernatants (112:1 and 28:1, respectively, P less than 0.01). Arachidonate stimulation increased 6-keto-PGF1 alpha and TXB2 levels similarly in the intact vein effluent. In contrast, stimulation of the venous rings resulted in a relatively larger increase in TXB2 than in 6-keto-PGF1 alpha. This caused 6-keto-PGF1 alpha to TXB2 ratio to decline (p less than 0.01). The identity of TXB2 was confirmed in several different ways. These data suggest that 1) human umbilical veins produce TXA2 in addition to PGI2, 2) TXA2 release is more by venous rings than by the intact vein probably reflecting contribution from non-endothelial layers, and 3) arachidonate stimulation causes relatively greater release of TXA2 than of PGI2 from the venous rings, whereas release of PGI2 and TXA2 is similar from the intact vein.

6-Ketoprostaglandin F1 alpha↗