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Biomedical subjects

M Lemieux

Publications and source records attributed to M Lemieux.

17 recordsLinked to original sources

Haemodynamic and abdominal motor reflexes elicited by neurotensin in anaesthetized guinea-pigs.

1. Single intraperitoneal (i.p.) injections of neurotensin (NT) (0.14- 140 nmol kg-1) in anaesthetized guinea-pigs were found to trigger transient abdominal wall contractions (TAWC) accompanied by relatively sustained increases of systemic blood pressure (BP) and heart rate (HR). The modification of the latter NT effects by various drugs and surgical manipulations was examined to obtain some insight into the nature of, and possible relationship between, these responses. 2. The abdominal motor response (i.e. TAWC) to i.p. NT (14 nmol kg-1) was inhibited by prior i.v. injection of the guinea-pigs with pancuronium (0.27 mumol kg-1), morphine (1.5 and 15 mumol kg-1), clonidine (0.34 mumol kg-1), by concomitant i.p. injection of procaine 2% w/v, or by acute spinalization. It was potentiated by naloxone (2.8 and 28 mumol kg-1), but not affected by i.v. injection of autonomic drugs (i.e. pentolinium, prazosin, yohimbine and atropine), by capsaicin desensitization, or by acute bilateral cervical vagotomy. In spinalized animals a sustained abdominal wall contraction (SAWC) was unmasked, which was resistant to i.v. morphine, clonidine or baclofen but suppressed by i.v. pancuronium or i.p. lignocaine 2% w/v. 3. Haemodynamic responses to i.p. NT were not affected by i.v. pancuronium, morphine, naloxone, atropine, or by vagotomy. They were inhibited by i.v. pentolinium or clonidine (BP, HR), i.v. prazosin (BP), i.p. procaine 2% w/v (BP, HR), capsaicin desensitization or acute spinalization (BP, HR). Yohimbine (i.v.) potentiated BP and HR increases caused by i.p. NT.4. These results suggest that: (1) the haemodynamic and TAWC responses to i.p. NT in this animal model, are two independent, neurally-mediated reflexes which are likely to originate from the abdominal cavity and require a functionally intact spinal cord for their full expression; (2) the neural pathways subserving both types of responses appear to be different from each other. The nature and time-response characteristics of the reflexes caused by i.p. NT, raise the possibility that i.p. NT is a noxious stimulus, at least in guinea-pigs.

Animals

Validation and applications of mitral prosthetic valvular areas calculated by Doppler echocardiography.

Doppler echocardiography is used in the noninvasive evaluation of mitral valve prostheses using parameters heretofore validated primarily for native valves. Accordingly, this study was designed to examine the validity and relative usefulness of valve gradient and area measurements in a group of 26 patients (17 women, 9 men, mean age 62 +/- 8 years), 19 +/- 4 months after implantation of different sizes (25 to 31 mm) of a given type of bioprosthesis. Areas obtained with both the continuity equation, using stroke volume measured in the left ventricular outflow tract, and the pressure half-time method are compared to known prosthetic areas derived from an in vitro hydraulic model. Areas calculated by the continuity equation correlate well with in vitro areas (r = 0.82, standard error of the y estimate = 0.1 cm2, p less than 0.001), and are within the range of predicted in vitro values in 92% of cases. Areas derived by the pressure half-time method do not correlate with in vitro areas (r = 0.15, p greater than 0.3) or continuity equation areas (r = 0.23, p greater than 0.2), and are above the range of predicted values in 69% of cases. Correlations are also found between continuity equation areas and the peak and mean valvular gradients (r = 0.59, p less than 0.005 and r = -0.63, p less than 0.0005, respectively). Taking the effect of cardiac output on gradients into account results in projected relations between indexed prosthetic areas and the pressure gradients at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

An antigen located in the kinetochore region in metaphase and on polar microtubule ends in the midbody region in anaphase, characterised using a monoclonal antibody.

We describe a new component of the kinetochore region of Chinese hamster ovary cells, which was characterised using a monoclonal antibody (mAb). This antigen was localised on the kinetochore regions of purified metaphase chromosomes, but in anaphase it was instead located on the polar microtubules in the midbody region, where they terminate in the stembody. It was not detectable in prophase or interphase cells by immunofluorescence, but was present in the interphase nucleus as shown by immunoblotting after SDS-polyacrylamide gel electrophoresis. The mAb recognised two polypeptides of Mr 140,000 and 155,000. The localisation of this antigen in metaphase on the kinetochore region, where the plus ends of the kinetochore microtubules are temporarily stabilised when they attach, and later in the stembody and midbody where the plus ends of the polar microtubules are stabilised in anaphase and telophase, suggests that it could play a role in stabilising the plus ends of microtubules and thus in the control of microtubule dynamics during mitosis.

Anaphase

Validation and applications of indexed aortic prosthetic valve areas calculated by Doppler echocardiography.

Doppler echocardiographic evaluation of aortic valve prostheses is based on the use of variables heretofore validated mostly for native valves. Accordingly, this study examined the validity and relative usefulness of the Doppler valve gradient and area measurements in 31 patients (mean age 69 +/- 10 years) 20 +/- 4 months after implantation of a given type of aortic bioprosthesis ranging in size from 19 to 29 mm. Valve area data obtained with both the standard and simplified continuity equations were compared with known in vitro prosthetic valve area measurements and an excellent correlation was obtained between the standard and simplified continuity equations (r = 0.98, SEE +/- 0.07 cm2, p less than 0.0005) and between in vivo and known in vitro prosthetic valve areas (r = 0.86, SEE +/- 0.16 cm2, p less than 0.0005). Peak gradient ranged from 10.8 to 75.0 mm Hg (mean 35 +/- 16) and mean gradient from 7.6 to 43.7 mm Hg (mean 20.5 +/- 9.5). The correlations between prosthetic valve gradient and in vivo area were r = -0.53, SEE +/- 14 mm Hg and r = -0.49, SEE +/- 8.63 mm Hg for peak and mean gradient, respectively. These relations were improved by indexing valve area by body surface area. The best correlations were obtained between indexed valve area and a quadratic function of the gradient (r = -0.72, SEE +/- 11.72 mm Hg and r = -0.70, SEE +/- 7.28 mm Hg for peak and mean gradient, respectively), reflecting a curvilinear relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Value of a cinefluoroscopic assessment of the Lillehei-Kaster prosthetic heart valves.

In order to assess the functioning of the pivoting disc of the Lillehei-Kaster prosthetic valve, a cinefluoroscopic technique using multiple angulations was developed. The disc was detected in 240 (99%) of the 242 valves studied (126 aortic, 107 mitral, and nine tricuspid valves). The maximal-opening angle of the disc was measured in 75% of the aortic but only 20% of the mitral valve prostheses in the 182 valve studies in which this was attempted. Prosthetic dysfunctions were suspected clinically in three aortic and three tricuspid valves and confirmed with the cinefluoroscopic technique. This cinefluoroscopic approach constitutes a rapid, noninvasive, and sensitive evaluation of the function of the Lillehei-Kaster prosthetic valve in the aortic position.

Aortic Valve

Mediastinopleuroscopy: a new approach to the diagnosis of intrathoracic diseases.

With the advent of modern therapy, it has become essential to obtain a tissue diagnosis in all cases of pulmonary and mediastinal disease. Since it is often necessary to resort to thoracotomy as a final step in making such a diagnosis, we have sought a procedure that is simpler while capable of providing the same information. Through a standard cervical mediastinoscopy incision, the mediastinum is first explored; if the diagnosis is not obtained, the mediastinal pleura is digitally opened and lung or pleural biopsies are taken. In the course of 1,100 mediastinoscopies since 1969, 275 pleuroscopies have been done. We were able to obtain a tissue diagnosis in 102 (78%) of 131 patients with bronchogenic carcinoma, in 92 (91%) of 102 with benign pulmonary disease, and in all 20 (100%) with pleural disease.

Biopsy, Needle

Local application of neurotensin to abdominal organs triggers cardiovascular reflexes in guinea pigs: possible mechanisms.

Intraabdominal (IAB) injections or topical application of neurotensin (NT) to the serosal surface of the ileum or stomach evoked dose-dependent increases of blood pressure and of heart rate in anesthetized guinea pigs. These effects were markedly reduced by prior animal treatment with a ganglion blocker, alpha and beta adrenoceptor blockers, as well as by exposure of the abdominal organs to lidocaine, a local anesthetic. The blood pressure and heart rate responses to IAB injections or topical application of NT to the ileum or stomach were both inhibited by animal pretreatment with capsaicin. Cervical vagotomy or atropine pretreatment did not prevent or alter the cardiovascular responses to IAB injections of NT. These results suggest the presence in some organs and/or tissues of the abdominal cavity of sympathetic, capsaicin-sensitive sensory nerve fibers which, upon stimulation by NT, produce reflex increases of blood pressure and of heart rate.

Administration, Topical

Capsaicin-sensitive primary afferents are involved in the hypotensive effect of neurotensin in ganglion-blocked guinea pigs.

The mechanism of the blood pressure (BP)-lowering effect of neurotensin (NT) in the anesthetized, ganglion-blocked guinea pigs was further examined using animals in which the basal BP was artificially raised by an IV infusion of noradrenaline (NA) to overcome the BP-lowering effect of the anesthesia as well as of the ganglion blocker. The animals were also vagotomized and given atropine at the beginning of the experiments to prevent potential baroreceptor-mediated vagal reflexes and/or activation of muscarinic receptors by endogenous acetylcholine. Under these experimental conditions, the IV bolus injections of NT as well as of capsaicin (a reference drug) produced dose-dependent hypotensive effects and variable levels of tachycardia. Omitting the ganglion blocker from the animal drug regimen attenuated but did not abolish the BP-lowering effect of NT and of capsaicin. Neither the hypotensive nor the tachycardic effects of NT and of capsaicin in ganglion-blocked guinea pigs were affected by prior animal treatment with propranolol (a beta adrenoceptor blocker), antihistaminics (mepyramine, cimetidine) or indomethacin (a cyclooxygenase inhibitor). Morphine was found to slightly reduced the hypotensive effect of NT without altering its slight tachycardic effect. Both the hypotensive and tachycardic effects of NT and of capsaicin, in contrast to those elicited by substance P (SP) and calcitonin gene-related peptide (CGRP), were inhibited in ganglion-blocked guinea pigs pretreated four days previously with capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways

Effect of initial blood pressure level on cardiovascular reflexes caused by intraperitoneal neurotensin.

The reflex changes of systemic blood pressure (BP) and heart rate (HR) induced by intraperitoneal (IP) injections of neurotensin-containing solutions (NTCS) were measured in anesthetized guinea pigs whose BP was raised up by intravenous (IV) infusions of either angiotensin II (ATII) or noradrenaline (NA), and compared to those observed in control animals (i.e., saline-infused guinea pigs with low initial BP level). The amplitudes of reflex pressor and tachycardic responses to IP NTCS were either not affected or reduced in animals whose BP was raised with ATII or NA. However, no hypotensive effect was observed, following IP NTCS, in any of the animals tested. The results indicate that high initial BP levels tend to attenuate the reflex increases of BP and HR caused by IP NTCS, the level of inhibition being largely determined by the type of vasopressor agent utilized to raise up the BP. They also suggest that the initial BP level is unlikely to be an important factor in determining whether the activation of capsaicin-sensitive visceral afferents will produce hypotensive or hypertensive effects in this animal model.

Angiotensin II

Further observations on the mechanism of the cardiovascular reflexes caused by exposure of the peritoneum to neurotensin.

Intraperitoneal (IP) injections of either 1, 3 or 9 ml of neurotensin-containing solutions (NTCS) with 5.4, 54, 540 or 5400 nM of neurotensin (NT) were found to cause concentration-dependent, but volume-independent, increases of blood pressure (BP) and heart rate (HR) in anesthetized, close-abdomen guinea pigs. The duration of both effects varied between 15 to 30 min depending both on the NT concentration and volume of NTCS utilized. Indirect evidence suggested that NT inactivation within the peritoneal cavity contributed to shorten the duration of NT effects. Animal pretreatment with a ganglion blocker, adrenoceptor antagonists, clonidine or capsaicin, reduced the BP and HR increases caused by IP injection of NTCS whereas both effects were either unaffected or slightly potentiated by animal pretreatment with atropine, morphine or captopril. Addition of a local anesthetic to NTCS inhibited the hemodynamic effects of NT whereas acute bilateral cervical vagotomy was without significant effect. These results suggest that NT has the ability to trigger cardiovascular reflexes following its IP injection in guinea pigs. The activation of peritoneal, sympathetic, capsaicin-sensitive primary afferents appears to be at the basis of these reflexes, the amplitudes of which seem poorly related to the volume of NTCS utilized (at least within the range of volume examined).

Animals

Mechanism of the pressor response to intraperitoneal injection of bradykinin in guinea pigs.

Single intraperitoneal (IP) injection of bradykinin (BK) in anesthetized guinea pigs caused concentration-related pressor effects and slight, not significant tachycardia. Intravenous injections of BK in the same animal model evoked hypotension and a marked tachycardia. IP injection of des-Arg9-BK, a selective B1 receptor agonist, caused no changes of blood pressure or heart rate. The pressor response to IP BK was reduced by concomitant IP injection of lidocaine or of D-Arg[Hyp3,D-Phe7,Leu8]BK, a B2 receptor antagonist. It was also inhibited by acute animal pretreatment with sympatholytic drugs, by chronic animal exposure to capsaicin, or acute spinalization, but it was not affected by atropine, propranolol, indomethacin, [Leu8]des-Arg9-BK, a B1 receptor antagonist, or by acute cervical vagotomy. These results suggest that pressor responses to IP BK in anesthetized guinea pigs are reflex in nature, involving abdominal, capsaicin-sensitive, nonvagal visceral afferents, efferent components of the sympathetic nervous system and possibly supraspinal centers, and likely to be mediated by B2 receptors of kinins presumably located on abdominal visceral afferents.

Animals

Behavioral responses elicited by intraperitoneal neurotensin in guinea pigs.

The potential behavioral responses to single intraperitoneal (IP) injection of neurotensin (NT) were examined in conscious, freely moving guinea pigs. Most animals injected with NT solvent (i.e., controls) or NT solution with low NT concentration (i.e., 5.4 nM) exhibited little or no particular behavioral reaction. On the other hand, 50 to 75% of the animals given IP injection of NT with 54, 540, or 5400 nM of NT exhibited motor responses characterized by a transient episode of clonic body jerks. Vocalization responses were observed in less than 25% of the animals given IP NT. Animal pretreatment with morphine reduced the incidence of motor and vocalization responses. The results were interpreted as an indication that IP injection of moderately concentrated NT solution (i.e., greater than or equal to 54 nM) is probably a weak noxious stimulus in conscious guinea pigs.

Animals