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Biomedical subjects

M A Morales

Publications and source records attributed to M A Morales.

At least 19 recordsLinked to original sources
PubMed1995

Vasorelaxant effect of the analgesic clonixin on rat aorta.

1. A novel vasorelaxant effect of clonixinate of L-lysine (Clx), analgesic and anti-inflammatory, was studied in rat aortic rings. 2. Clx completely relaxed aortic rings contracted by KCl 70 mM and together with its analog flunixin exhibited lesser potency but equal efficacy than verapamil. In comparison, indomethacin, which is a more potent cyclo-oxygenase inhibitor relaxed only about 40% of the maximal contraction of aortic rings. 3. Furthermore, Clx antagonized Ca2+ dependent aortic contraction and BAY K-8644 induced aortic contraction suggesting its calcium antagonist character. 4. From these results it can be concluded that the hypotensive effect seen in rats in vivo after Clx i.v. injection arises because of vasodilatory effect of Clx and gives further support to the proposal that the pharmacological mechanism of action of Clx should be calcium antagonism.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Effects of clonixin on the electrical activity of cardiac pacemaker cells.

1. The electrophysiological effects of clonixin, a non-steroidal analgesic, on cardiac pacemaker cells of spontaneously beating frog sinus venosus, were studied by intracellular recording of transmembrane potentials. 2. Results show that clonixin (Clx) between 1 x 10(-6) M and 3 x 10(-4) M, decreases the OS, APA, Vmax and frequency of primary and subsidiary cells, however pacemaker cells differ in their sensitivity to Clx. 3. At 2 x 10(-6) M, Clx completely blocked the spontaneous beating of primary cells. It is necessary to increase the Clx concentration about two orders of magnitude in order to attain a similar degree of blockade of subsidiary cells. 4. Previous or simultaneous superfusion with atropine does not modify Clx effects, thus a probable cholinergic mechanism of action for Clx is discarded. 5. When Clx concentrations were lower than 5 x 10(-4) M, their effects on both types of cells were partially reversed by a 100% increase of external calcium concentration. 6. BAY K-8644 which stimulates calcium influx through calcium L-type channels, reverted Clx effects on pacemaker cells. 7. It is suggested that Clx blocks calcium inward current which generates all or part of the upstroke of primary cells and subsidiary ones, respectively.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Use-dependent fade and slow recovery of long-term potentiation in superior cervical ganglion of the cat.

1. In anesthetized cats under partial block of nicotinic ganglionic transmission by hexamethonium and in which the cervical sympathetic trunk (CST) was split into two bundles of approximately equal size, a 40-Hz 5-s conditioning stimulus train to one bundle produced prolonged potentiation of the postganglionic compound action potential evoked by a test stimulus to the same or to the other bundle [homosynaptic and heterosynaptic, respectively, long-term potentiation (LTP)]. The LTP was detected also by recording the nictitating membrane (NM) contraction in response to a test preganglionic train. 2. The homosynaptic or heterosynaptic LTP produced by applying the conditioning 40-Hz 5-s train to one bundle was markedly depressed in amplitude and duration after stimulation of that bundle at 40 Hz for 20 min, whereas the homosynaptic or heterosynaptic LTP produced by applying the conditioning 40-Hz 5-s train to the other bundle was unchanged. The latter evidence suggests that all superior cervical ganglion (SCG) synapses can still express LTP during the depression that follows the 40-Hz 20-min train. 3. In 4 h there was no appreciable recovery of LTP from the depression produced by a 40-Hz 20-min train (n = 5). However, after 3 days (n = 3) and 5 days (n = 3), LTP recovered to 53 and 90% of control, respectively. 4. When colchicine was applied to the CST bilaterally, at a concentration sufficient to block fast axonal transport, and one CST only was stimulated for 20 min at 40 Hz, the LTP recorded 4 days later was significantly smaller on the stimulated than on the contralateral, control, side.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Modulated long-term potentiation in the cat superior cervical ganglion in vivo.

In the sympathetic ganglion a high frequency conditioning train produces a post-train potentiation (PTrP) which decays with a temporal course that can be described by two components: an early faster component known as post-tetanic potentiation (PTP), and a long-lasting one which is known as long-term potentiation (LTP). The magnitude of PTP and LTP is thought to be a function of the subliminal fringe size. Moreover, under full activation of ganglion cells LTP does not appear due to the saturation conditions. LTP emerges only when the subliminal fringe is increased, and to achieve this, a low-level tetanization must be performed. However, another possibility, explored in this paper, is that in addition to the desaturation effect of the low-level conditions of tetanization, a different mechanism, responsible for the LTP appearance, may be introduced by these low-level conditions of tetanization. This possibility implies a variable LTP according to the input conditions; accordingly, the shape of LTP was compared in 4 experimental conditions in which the input to the ganglion cells was different; (1) supramaximal activation of the intact cervical sympathetic trunk (CST), (SPM); (2) submaximal activation of the intact CST, (SBM); (3) supramaximal activation of the partially transected CST, (TRN): and (4) supramaximal activation of the intact CST under partial nicotinic block with hexamethonium. (BLK). Even when PTrP was evoked with the same subliminal fringe obtained under the 3 low-level conditions of tetanization, the degree of potentiation and the proportion of PTP and LTP were different. After either SPM or SBM conditions LTP was negligible, though PTP developed to a certain degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Screening for antibodies against infectious bronchitis virus: specificity of the haemagglutination inhibition test.

A screening of antibodies against strain M-41 and the Dutch variant strains D-274 and D-1466 of infectious bronchitis virus (IBV) using the haemagglutination inhibition test (HI) was carried out in Chile. The presence of these variant strains has not been reported yet and therefore the probability of finding positive flocks is low. On this basis some statistical analysis were made with those data obtained in order to contribute to the problem of the specificity of the HI test for IBV diagnosis. All sera were distributed in different categories of possible results against each strain according with the HI titre obtained and employing different discrimination levels for a positive or negative status against IBV. It was concluded that discrimination levels varying from 4.0 to 5.0 log2 are useful for establishing the presence or absence of antibodies against IBV but if a serotype specific diagnosis is needed, then the discrimination level should be elevated, specially when secondary immune responses are measured.

Animals↗
PubMed1989

Effects of 7-O-demethylisothalicberine, a bisbenzylisoquinoline alkaloid of Berberis chilensis, on electrical activity of frog cardiac pacemaker cells.

1. In spontaneously beating preparations of sinus venosus of the chilean frog Caudiverbera caudiverbera, the electrophysiological effects of 7-O-demethylisothalicberine (7-O-DI) on transitional pacemaker cells were investigated. 2. 7-O-DI in concentration 1 x 10(-4) M blocked the action potential of transitional cells. This blockade was preceded by subthreshold oscillations and depolarization of membrane potential. 3. Lower concentration of the drug to induce complete blockade (5 x 10(-5) M), allowed to observe a great depression of bioelectric cell characteristics in transitional fibres. 4. 7-O-DI induced blockade of transitional cells action potential was preceded by the appearance of a notch in their upstroke and the persistence of a fast depolarizing activity that remained unblocked. This 7-O-DI resistant fast component of the upstroke was blocked by tetrodotoxin. 5. Transitional cells completely blocked by 7-O-DI were depolarized to about 40 mV. 6. The results indicate a close similarity between 7-O-DI and verapamil effects on action potential configuration.

Action Potentials↗
PubMed1987

Oral isosorbide 5-mononitrate can protect from myocardial ischemia induced by ergonovine test and by isometric effort. Preliminary results from an echocardiographic acute study in anginal patients.

Isosorbide 5-mononitrate (IS 5-MN) has favourable pharmacodynamic properties, such as the specific half-life (close to 5 h) and the bioavailability (100% after oral ingestion). The efficacy of IS 5-MN (20 mg t.i.d.) in the treatment of stable angina has been documented in previous studies. In the present acute study, two subsets of patients were evaluated: the first group consisted of 10 patients with coronary vasospasm in whom oral IS 5-MN was effective in preventing myocardial ischaemia due to an abrupt reduction in coronary blood flow; the second group regarded 8 patients with a mixed form of angina, where the responsible mechanism for ischaemia can be considered a combination of increased myocardial oxygen demand and reduction of coronary blood flow due to vasoconstriction of large vessels. In all these patients, IS 5-MN was able to protect against transient myocardial ischaemia induced by isometric test. In conclusion, from the data available in our studies, IS 5-MN appears to be a useful drug in anginal patients: the beneficial effect is likely based on its capability both to prevent the abnormal vasoconstriction of diseased coronary vessels and to reduce myocardial oxygen demand.

Administration, Oral↗
PubMed1986

A synaptic model for the kindling effect.

In this work we present a model of the kindling effect based on the Hopf bifurcation for a system of ordinary differential equations. The model shows how quantitative changes in the physiological parameters at the microscopic, synaptic scale, produce the afterdischarge which is a macroscopic effect at the neuronal network scale. The presynaptic mechanisms are based on the vesicular hypothesis, or more generally on the quantal theory of synaptic transmission. The postsynaptic processes rely on Granit's law. This model gives a consistent framework which organizes and explains several experimental observations.

Animals↗
PubMed1986

Dipyridamole-echocardiography test in angina at rest: noninvasive assessment of coronary stenosis underlying spasm.

In a previous study performed in patients with effort angina pectoris, we showed that the dipyridamole-echocardiography test (DET) is feasible and useful for the detection of coronary artery disease. The positivity of the test (consisting of two-dimensional echocardiography [2 DE] combined with dipyridamole infusion [0.14 mg/kg/min for 4 minutes]) is linked to the appearance of regional asynergy. In the present study, DET and exercise stress test (EST) were performed in 62 patients with angina at rest in the active phase. The overall sensitivity of DET and EST for the detection of coronary artery disease was 62% and 83%, respectively (p less than 0.05); the specificity of DET and EST was 100% and 64%, respectively (p less than 0.05). In 10 DET-positive patients, a spontaneous attack was also monitored by 2DE; the myocardial wall involved by ischemia was invariably the same both in patients with spontaneous and in those with dipyridamole-induced ischemia. Thus, in our population of patients with angina at rest (in whom an important functional component is also likely to be present during exercise), DET was significantly less sensitive but significantly more specific than EST in detecting coronary artery disease.

Adult↗
PubMed1986

The therapeutic role of isosorbide-5-mononitrate+ in stable and unstable angina pectoris.

Various studies on the pharmacodynamic and clinical properties of isosorbide-5-mononitrate (IS-5-MN) indicate that this drug is effective in the treatment of stable angina pectoris. Acute and chronic studies, in fact, show an improved performance and an amelioration of the clinical status in patients under treatment. On the other hand, acute studies on vasospastic and mixed angina, two common clinical manifestations of coronary artery disease, have demonstrated the capability of IS-5-MN in preventing episodes of transient myocardial ischemia. In analogy with other forms of nitrates, it is clear that IS-5-MN has a positive effect both on the coronary tree (preventing vasoconstriction) and on those hemodynamic parameters which influence the myocardial oxygen demand (reducing myocardial oxygen consumption). Further information is needed, however, to clarify the issue of tolerance development after chronic administration; so far it appears that tolerance may develop when patients are treated with doses of IS-5-MN greater than 20 mg t.i.d.. On the basis of the clinical studies carried out with IS-5-MN, and its favourable pharmacological profile, it is foreseeable that this drug will have an increasing role in the treatment of angina pectoris.

Angina Pectoris↗
PubMed1986

Echocardiography in the study of myocardial ischemia in man: the clinical model of Prinzmetal's angina.

Standard echocardiography was employed to study the clinical model of myocardial ischemia with ST-segment elevation, well known as Prinzmetal's angina. Ultrasonic monitoring was performed during the appearance of ST-segment elevation, from onset of pain, during an ergonovine maleate test, hemodynamic monitoring, radioisotopic studies and, occasionally, during routine examinations, when spontaneous episodes occurred. Reliability of findings was supported by two important conditions: each patient acted as his own control, since recording was carried out from basal state to basal state, throughout ischemia, or from ischemia to basal state; behaviour of ischemic walls was compared with that of non-ischemic ones. Echocardiographic findings in acute myocardial ischemia were similar both in spontaneous and in induced episodes and were mainly characterized by: decrease in contractility indices of the ischemic segment, such as wall motion and percent systolic thickening; increase in left ventricular end-systolic and end-diastolic diameter, with a decrease in percent fractional shortening; distorted shape of ventricular cavity, transiently deformed as in a "functional" aneurysm; a sharp demarcation between ischemic and non-ischemic adjacent segment, "step sign", was present only in severe cases. Taking ST-segment elevation as a reference the time sequence of events was studied, correlating mechanical, electric and clinical markers of ischemia. At least three different echocardiographic phases were identified in the evolution of ischemic attacks: Pre-electrocardiographic phase, when mechanical impairment is detected by ultrasounds in the absence of both ST-segment changes and pain; Electrocardiographic phase, when echocardiographic signs of ischemia co-exist with obvious electrocardiographic signs.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris, Variant↗
PubMed1986

Echocardiographic documentation of myocardial ischemia in presence of angina pectoris without ST-T changes.

A frequent clinical problem is to document the elusive entity of electrocardiographically silent myocardial ischemia. Since echocardiography offers a practical tool to detect reversible mechanical changes due to ischemia, 32 patients with angina on effort, and coronary artery disease, and 15 patients with angina at rest were studied. In all 47 patients electrocardiographic changes during effort or rest pain were inconclusive. Combined 12 lead electrocardiographic and 2-Dimensional echocardiographic monitoring were performed: during ergonovine testing in the 15 patients with angina at rest; during dipyridamole testing in the 32 patients with effort angina and a non diagnostic stress test. Interpretable echocardiograms were obtained in all the patients studied. Positivity of both the Ergonovine-Echocardiographic test and the Dipyridamole-Echocardiographic test was based upon the detection of regional transient asynergy. Of the 15 patients who had chest pain at rest in the absence of diagnostic electrocardiographic changes, Ergonovine-Echocardiographic test was positive in 6 (40%). Of the 32 patients who had chest pain in absence of diagnostic electrocardiographic changes during exercise stress testing, the Dipyridamole-Echocardiographic test was positive in 18 (56%). Echocardiographic monitoring in combination with provocative testing (ergonovine and dipyridamole) may be a practical, non invasive, inexpensive tool which is feasible in all patients with good basal echocardiograms and is able to unmask electrocardiographically silent myocardial ischemia by providing objective mechanical evidence of the ischemic event.

Adult↗
PubMed1985

Dipyridamole-echocardiography test in effort angina pectoris.

This study assesses the clinical feasibility and usefulness of dipyridamole infusion for the detection of coronary artery disease (CAD) by using 2-dimensional echocardiography (2-D echo) and 12-lead electrocardiographic monitoring. Dipyridamole infusion (0.14 mg/kg/min for 4 minutes) was performed in 66 consecutive patients with effort chest pain and in 9 control subjects. Among the 28 patients with positive dipyridamole-echocardiography test responses, 18 had diagnostic electrocardiographic changes (ST-segment depression on anterolateral leads), but these changes were unrelated to the site of asynergy. The dipyridamole-echocardiography test had an overall sensitivity of 56% and specificity of 100% for the presence of CAD. Exercise stress testing (EST) had an overall sensitivity of 62% and a specificity of 80%. Thus, the dipyridamole-echocardiography test, which is feasible in essentially all patients with good basal echocardiograms, has a lower overall sensitivity in detecting CAD than EST but a higher specificity, detects the site of apparent ischemia as identified by regional asynergy more precisely than EST, and can unmask electrocardiographically silent effort ischemia.

Adult↗
PubMed1985

Transient myocardial ischemia with minimal electrocardiographic changes: an echocardiographic study in patients with Prinzmetal's angina.

Kn patients with Prinzmetal's angina, episodes of transient T wave abnormalities (T abn) are often documented in addition to the typical episodes of ST segment elevation (ST). As the interpretation of these minor ECG changes is still uncertain, we investigated if transient T abn are associated with reversible ventricular asynergies, similar to episodes with ST. For this purpose an ECG lead and a two-dimensional echocardiographic projection, which showed clear-cut changes during previous episodes of ST, were simultaneously monitored in five patients with Prinzmetal's angina for a total of 13 hours and 20 minutes. In all patients, the 30 episodes of ST recorded were all accompanied by reversible ventricular asynergies. Furthermore, in four of these patients, 14 episodes of T abn (peaking, flattening, or the appearance of a diphasic T wave) were recorded. All T abn were associated with reversible asynergies, as detected by three independent observers. The mechanical impairment occurred in the same ventricular wall both during ST and during T abn. During T abn the degree of mechanical impairment appeared less severe (hypokinesia in 12 and akinesia in two episodes) than during ST (hypokinesia in one, akinesia in 25, and dyskinesia in four episodes) (p less than 0.001). The duration of asynergies was less during T abn (107 +/- 76 seconds) than during ST (169 +/- 83 seconds) (p less than 0.05). Chest pain was reported in 5 of 14 episodes of T abn (36%) and in 20 of 30 (66%) episodes of ST (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Transient changes in left ventricular mechanics during attacks of Prinzmetal's angina: an M-mode echocardiographic study.

M-mode echocardiograms were recorded in 12 patients with Prinzmetal's angina during 29 episodes of transient myocardial ischemia at rest (18 spontaneous and 11 ergonovine-induced). At peak ST segment elevation a regional mechanical impairment was observed in the interventricular septum during 23 episodes of angina and in the posterior wall during six episodes. In the 18 spontaneous episodes the left ventricular ischemic wall, when compared to the basal state, was found to have a significant reduction in motion (-76.3 +/- 9.1%) (mean +/- SEM), in diastolic thickness (-11.7 +/- 2.5%), and in percent systolic thickening (-88.0 +/- 5.6%). Increase in left ventricular end-diastolic diameter (+13.1 +/- 2.1%) and decrease in percent fractional shortening (-38.1 +/- 3.7%) were also observed. When ST segment was back to the isoelectric line, a transient overshoot in regional left ventricular function was observed. In induced episodes statistically significant changes could be detected by M-mode echocardiography even before appearance of ST segment elevation and anginal pain. No significant difference was found in type or degree of mechanical impairment between induced and spontaneous episodes. Therefore, in patients with Prinzmetal's angina: (1) M-mode echocardiography allows detection of mechanical changes due to transient myocardial ischemia; and (2) mechanical impairment occurs earlier than clinical (pain) and electrocardiographic (ST segment elevation) signs of transmural ischemia.

Adult↗
PubMed1984

Transient changes in left ventricular mechanics during attacks of Prinzmetal angina: a two-dimensional echocardiographic study.

Fifty-five ischemic attacks at rest with ST segment elevation were recorded by two-dimensional echocardiography (2DE) in 20 patients with Prinzmetal angina. Eighteen ischemic attacks were recorded starting from intravenous injection of ergonovine maleate while 37 spontaneous ischemic attacks were recorded from onset of either anginal pain or ECG changes or from the basal state. In each ischemic attack at least one of the following transient alterations was observed by 2DE during ST elevation: (1) Regional hypokinesia, akinesia, or dyskinesia; (2) "step sign," that is, a sharp demarcation between an akinetic or dyskinetic area and an adjacent normal or hypercontracting region; and (3) geometric changes in left ventricular shape, that is, globular appearance in diastole and hourglass silhouette in systole. Regional myocardial asynergy was detected earlier than onset of pain (which was not present in 21 [38%] ischemic episodes) or ST segment elevation on ECG, as documented in 40 ischemic episodes (16 induced and 24 spontaneous) in which echocardiographic monitoring was performed from basal state and carried on up to the appearance of ischemia. All described mechanical changes were fully reversible after pain subsided and ST segment was back to isoelectric, either spontaneously or with nitrates; furthermore, a contractile "rebound phenomenon" of the previously ischemic wall was observed in some episodes. In conclusion, these results outline a role for 2DE in detecting cardiac mechanical impairment due to transient myocardial ischemia with ST segment elevation in humans.

Adult↗