Biomedical subjects

J M Pinto

Publications and source records attributed to J M Pinto.

At least 19 recordsLinked to original sources

PubMed1992

Transient coronary stenosis associated with arrhythmia and ischemia 24 hours after reperfusion.

We examined the electrophysiologic sequelae of transient reductions in coronary blood flow (CBF) in conscious dogs. Animals were instrumented to measure arterial pressure, heart rate, repetitive extrasystole threshold (RET), and CBF before coronary stenosis, during 90 minutes of a 50% reduction in CBF, and at 1, 24, 48, and 72 hours after reperfusion. RET was decreased at 24 and 48 hours but returned to baseline by 72 hours after reperfusion. Frequent ventricular ectopic activity (VEA), absent during the control period, was noted during stenosis and at 1, 24, and 48 hours after reperfusion. beta-Adrenergic blockade (metoprolol) normalized the decreased RET at 24 hours. Addition of alpha 1-adrenergic blockade (prazosin) abolished VEA. Endocardial blood flow in the posterior papillary muscle of the left ventricle was reduced by 52 +/- 9% during stenosis, was similar to baseline levels by 1 hour after reperfusion, and decreased by 39 +/- 5% at 24 hours. We conclude that episodes of modest coronary artery stenosis may be followed by electrophysiologic changes indicative of increased vulnerability to malignant ventricular arrhythmias.

Animals↗

PubMed1992

Catecholamines in cerebrospinal fluid are increased by behavioral arousal and myocardial ischemia.

To study the central neural mechanisms involved in malignant ventricular arrhythmia, concentrations of norepinephrine in the cerebrospinal fluid were measured during behavioral stimulation and during coronary artery occlusion. Pigs were instrumented via thoracotomy with catheters to measure mean arterial pressure and plasma catecholamines and with silk snares around the left anterior descending coronary artery for occlusion after recovery from surgery. Cannulas were placed in the lateral ventricle of the brain to sample cerebrospinal fluid. Behavioral arousal was induced by lifting the pig in a canvas sling for 5 min. Mean arterial pressure, heart rate, and both plasma and cerebrospinal fluid norepinephrine concentrations increased significantly after lifting stimulation. In a separate experiment, 5 min after coronary artery occlusion, both plasma catecholamines and norepinephrine in cerebrospinal fluid were significantly elevated. Furthermore, pigs in which ventricular fibrillation occurred after occlusion had significantly higher concentrations of norepinephrine in cerebrospinal fluid before coronary artery occlusion.

Animals↗

PubMed1991

Diazepam administered prior to coronary artery occlusion increases latency to ventricular fibrillation.

Few studies have addressed the antiarrhythmic potential of pretreatment with diazepam in acute myocardial infarction. Thus, the effect of diazepam pretreatment prior to coronary artery occlusion was examined in conscious pigs. Animals were instrumented with aortic catheters to measure arterial pressure, a pulmonary artery catheter for drug administration, and a snare around the left anterior descending coronary artery for permanent occlusion one week later. Diazepam (1 mg/kg iv bolus) or vehicle was administered 10 minutes prior to occlusion. Eight of 14 animals receiving diazepam (57%) and 13 of 22 receiving vehicle animals (59%) developed ventricular fibrillation following coronary occlusion. However, the latency to ventricular fibrillation was significantly shorter (7 +/- 1 min) in animals receiving vehicle compared to animals receiving diazepam (11 +/- 1 min). Significant increases in heart rate were seen up to 5 hours after coronary occlusion only in animals receiving vehicle. The results indicate that diazepam pretreatment can increase ventricular fibrillation latency and prevent heart rate increases following acute myocardial infarction.

Animals↗

PubMed1991

Decreases in repetitive extrasystole threshold in the conscious pig with myocardial infarct were reversed by tyrosine.

Reports indicate that the administration of tyrosine, the precursor amino acid for catecholaminergic neurotransmitters, may be beneficial under conditions of physiologic stress. We studied the effects of tyrosine on vulnerability to ventricular arrhythmia in conscious pigs with healing myocardial infarcts, and sham operated (intact) pigs. Mean arterial pressure and heart rate were measured via chronically implanted aortic catheters. The repetitive extrasystole threshold (defined as the energy in milliamperes (ma) needed to cause a spontaneous ventricular beat following a premature beat induced by an electrical impulse), was measured via a bipolar pacing catheter placed during instrumentation surgery in the apex of the right ventricle. One week after infarct, the myocardial infarct group was studied before and ninety minutes after the administration of tyrosine (8 mg/kg iv). Before tyrosine, the myocardial infarct group had a significantly lower repetitive extrasystole threshold (12 +/- 1 ma) compared to the intact group (19 +/- 2 ma). Ninety minutes after tyrosine, the repetitive extrasystole threshold in the myocardial infarct group was 17 +/- 1 ma. The availability of tyrosine did not alter the repetitive extrasystole threshold in the intact group. Thus, vulnerability to ventricular arrhythmia was enhanced in pigs with recent myocardial infarction. Tyrosine, which can be nutritionally manipulated, may reduce myocardial vulnerability to arrhythmia after infarct.

Animals↗

PubMed1991

Decrease in repetitive extrasystole threshold during epinephrine infusion is enhanced in conscious dogs with perinephritic hypertension.

Hypertension is associated with myocardial hypertrophy as well as increased adrenergic responsiveness, both of which can predispose to malignant ventricular arrhythmias. This study was designed to test the effects of subpressor doses of epinephrine (0.15 and 0.3 micrograms/kg/min x 30 min) on vulnerability to ventricular arrhythmia in normotensive and perinephritic hypertensive dogs. Two groups of 6 dogs each were chronically instrumented with aortic catheters to measure mean arterial pressure and bipolar pacing catheters in the apex of the right ventricle to measure repetitive extrasystole threshold, an index of vulnerability to ventricular fibrillation. In the normotensive dogs, the low dose of epinephrine (0.15 micrograms/kg/min IV) had no significant effects on mean arterial pressure, heart rate of repetitive extrasystole threshold. However, in the hypertensive dogs, the same dose caused a significant 39% increase in heart rate (p less than 0.05) and 41% decrease in repetitive extrasystole threshold (p less than 0.05). These findings suggest that electrophysiological vulnerability of the myocardium caused by epinephrine infusion is enhanced in the hypertensive animal.

Animals↗

PubMed1991

Behavioral arousal enhances inducibility and rate of ventricular tachycardia.

Behavioral arousal may trigger malignant cardiac arrhythmias. To study the effect of arousal on ventricular tachycardia, pigs were instrumented with catheters to measure mean arterial pressure and sample plasma catecholamines and left anterior descending coronary artery snares for occlusion 1 wk later. Bipolar pacing catheters were placed in the right ventricular apex to induce ventricular tachycardia. One week after occlusion, electrophysiological testing was repeated before and immediately after arousal caused either by restraining and lifting the pig in a canvas sling or by bringing a stall mate into the room. The number of stimuli needed to induce monomorphic ventricular tachycardia was reduced by both types of arousal (P less than 0.05) compared with control conditions. Ventricular tachycardia rate was increased 60 +/- 17 beats/min after lifting stimulation (P less than 0.05). When beta 1-receptor blockade was induced by metoprolol, inducibility of ventricular tachycardia and rate were not different from control. Thus, in pigs, arousal may facilitate arrhythmogenesis. This effect may be mediated by sympathetic neural activity in the heart because it was annulled by beta 1-adrenergic blockade.

Animals↗

PubMed1990

Epinephrine-induced decrease in repetitive extrasystole threshold is reversed by tyrosine in conscious dogs.

Previous studies indicate that availability of L-tyrosine, the precursor for catecholaminergic neurotransmitters, reduced psychological and physiological effects of stressful situations including hypotension, cold and behavioral stress. The current study examined the effect of L-tyrosine administration on cardiac vulnerability to arrhythmia induced by an infusion of epinephrine in conscious dogs. Heart rate, mean arterial pressure and cardiac electrophysiologic parameters, i.e., effective refractory period and repetitive extrasystole threshold, were measured during infusion of epinephrine (0.3 micrograms/kg/min x 30 min), before and after L-tyrosine (B mg/kg iv bolus). Epinephrine administration significantly increased heart rate by 39% (p less than 0.05), and decreased repetitive extrasystole threshold by 33% (p less than 0.05). Mean arterial pressure and effective refractory period were unchanged. Following L-tyrosine, repetitive extrasystole threshold was restored to baseline levels. Tyrosine may thus ameliorate stress-induced increases in ventricular vulnerability to arrhythmias in conscious animals.

Animals↗

PubMed1990

Changes in ventricular fibrillation threshold during the development of perinephritic hypertension.

Established hypertension is associated with enhanced susceptibility to life-threatening arrhythmias. However, little is known about the effects of the development of hypertension on the electro-physiological properties of the heart. To study this relationship, dogs were chronically instrumented for recording mean arterial pressure and conducting cardiac electrical testing during right ventricular pacing using an intracavitary bipolar catheter. In normotension, ventricular fibrillation threshold was determined under alpha-chloralose anesthesia, after which perinephritic hypertension was induced by wrapping one kidney in silk followed by contralateral nephrectomy. During serial testing of the same animals, ventricular fibrillation threshold was significantly increased early in the development of hypertension (2 to 3 weeks after renal wrapping), but found to be significantly reduced at 6 to 7 weeks after renal wrapping. The increase in ventricular fibrillation threshold was eliminated by cholinergic blockade.

Animals↗

PubMed1989

Dietary supplementation of tyrosine prevents the rapid fall in blood pressure during haemorrhage.

Previous studies have demonstrated the ability of tyrosine (TYR), the amino acid precursor of catecholamines, to increase blood pressure in rats made hypotensive by haemorrhage. Other studies have shown that supplementation of the diet with TYR can reverse certain neurochemical and behavioural consequences associated with acute stress. Such studies demonstrate that during conditions of enhanced neuronal firing catecholamine synthesis is accelerated when additional precursor TYR is made available. In these situations the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase, activated via phosphorylation, becomes responsive to additional TYR. Our experiments were designed to study the ability of dietary TYR (3.7%, or 4X the normal amount), to prevent the rapid fall in blood pressure observed during acute haemorrhage. Rats consuming the high TYR diet (5 days) maintained arterial blood pressure (systolic, diastolic and mean) at significantly greater values during the period of acute haemorrhagic insult than animals maintained on a control diet. Rats fed the high TYR diet had significantly greater levels of the amino acid in the heart, adrenal glands, liver, kidney, brainstem, spleen and semimembranosus pars caudalis muscle. We conclude that TYR can be stored and most likely utilized in the synthesis of catecholamines for the maintenance of arterial blood pressure during acute haemorrhage. These results are of particular importance in light of the fact that most total parenteral nutrition solutions contain very little if any TYR.

Animals↗

PubMed1989

Abolition of clonidine's effects on ventricular refractoriness by naloxone in the conscious dog.

The interaction between opiate and adrenergic receptors on cardiac electrophysiologic function in the conscious dog was addressed in our study. We examined the effects of opiate receptor blockade with naloxone on clonidine-induced changes in refractoriness of the cardiac ventricle. Nine dogs were chronically instrumented for recording mean arterial blood pressure, administration of drugs and for measurement of effective refractory period of the ventricle. Clonidine (10 micrograms/kg, i.v.) significantly (p less than 0.05) decreased heart rate to 72 +/- 5 beats/minute from 108 +/- 8 beats/minute; mean arterial pressure decreased significantly (p less than 0.05) to 83 +/- 3 mmHg from 91 +/- 4 mmHg. Ventricular refractoriness was increased significantly (p less than 0.05) at current levels of 7 and 10 mA and pacing rates 180 and 200 beats/minute. Naloxone (3-10 mg/kg, i.v.) abolished clonidine's effects on heart rate, mean arterial pressure and ventricular refractoriness. We conclude that ventricular refractoriness may be regulated in part by interactions between central adrenergic and opioidergic systems.

Animals↗

PubMed1988

Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in mice.

An association has recently been proposed between the incidence of seizures and prolonged consumption of the phenylalanine-containing artificial sweetener, aspartame. Since consumption of aspartame, unlike dietary protein, can elevate phenylalanine in brain, and thereby inhibit the synthesis and release of neurotransmitters known to protect against seizure activity, the effect of oral doses of aspartame on the sensitivity of mice to the proconvulsant agents, pentylenetetrazole and fluorothyl was studied. Doses of aspartame were used which increased phenylalanine more than tyrosine in brain, as occurs in humans after the consumption of any dose of aspartame. Pretreatment with aspartame significantly increased the percentage of animals convulsing after administration of pentylenetetrazole and significantly lowered the CD50 for this convulsant. The average time to onset of seizures induced by fluorothyl in control mice was 510 sec; pretreatment with oral doses of 1000, 1500 and 2000 mg/kg of aspartame 1 hr earlier significantly reduced the time required to elicit seizures (394, 381 and 339 sec, respectively). The seizure-promoting effect of aspartame could be demonstrated 30, 60 or 120 min after the 1000 mg/kg dose. The seizures induced by either convulsant were potentiated by equimolar amounts of phenylalanine, a major endogenous metabolite of aspartame, while the other metabolites, aspartic acid and methanol, were without effect. Administration together with aspartame of the large neutral amino acid valine, which competes with phenylalanine for entry into the brain, completely abolished the seizure-promoting effect of aspartame.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Prostaglandin E2 gel compared to oxytocin for medically-indicated labour induction at term: a controlled clinical trial.

A clinical trial was carried out to compare the efficacy and tolerance of two modes of induction of labour: vaginally administered prostaglandin E2 gel vs intravenous perfusion of synthetic oxytocin. Fifty women with pregnancy at or near term in whom prompt vaginal delivery was clinically indicated were divided at random into sub-groups of 25 each. Initial dose of PGE2 gel was 1 mg followed by another application of 1 mg or 2 mg 6 hours later in case active labour stage has not been reached. Progressive oxytocin perfusion began with 1 mU/min., being increased gradually every 20 minutes until efficacious uterine dynamics were attained. Data were recorded on entry of age, parity, gestation age, cervical dilatation, Bishop score, indication for induction. Continuous materno-foetal monitoring was carried out during the induction period. Results were evaluated from induction/delivery time, type of delivery, maternal and foetal condition, and any side-effects which developed. Apart from a higher number of instrumental deliveries in the PGE2 gel series, which was not related to the induction method, there was no significant difference between any of the variables evaluated, both methods producing active labour in approximately 70% of the patients within 12 hours. The authors stress, however, the convenience, both for patients and hospital staff, of the administration of an intravaginal induction agent over a systemic therapeutic method of induction.

Administration, Intravaginal↗

PubMed1985

The impact of combined therapeutic modalities in head, neck, and esophageal cancer.

Nearly 50% of head and neck cancers and two-thirds of patients with esophageal cancer generally present late for initial treatment. The patterns of failure are generally locoregional with around 10% showing distant dissemination. Surgery alone and in combination with pre-operative radiation has not significantly increased salvage in these groups of cancer. The availability of increasingly effective drugs (Cisplatinum, MTX., Bleomycin), for head, neck and esophageal cancers have produced dramatic initial responses with excellent palliative relief of symptoms enabling adequate definitive radiotherapy or surgery for advanced T3, T4 lesions. Cisplatinum 20 mg/m2 daily X 5 - twice at the interval of 10 days with MTX 25 mg/m2 and Bleomycin 15 mg/m2 weekly X 2 have been used for T3 and T4 Head and Neck Cancers and Cisplatinum in the same dosage and MTX 200 mg twice in 10 days have been used for esophageal cancers. 88% responses in 35 patients have been noted in head and neck cancers and when the chemotherapy was followed by definitive radiotherapy, complete responses were achieved in 16 out of 25 patients (64%). This is a very significant response rate for T3, T4 cancers. Patients who were in a reasonably acceptable general condition after this regimen were further considered for two more courses of consolidative chemotherapy. Response rates in esophageal cancer was 78% (26 of 34 evaluable patients) - 6 of the 26 showed a complete response and all are alive from 8 months to 26 months. Our failure to obtain increasing cures at 3 and 5 years may be due to our ignorance of the capacity of dormant cells to proliferate, tumor cell kinetics, more effective use of chemotherapy or the biology of the host. These areas need further investigation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

PGE2 gel for enhancement of priming and induction of labour at term in patients with unfavorable cervix.

Fifty women (25 nulliparae and 25 multiparae) with unfavorable cervix at term were enrolled in a clinical experiment to evaluate the safety and efficacy of the intracervical application of 0.5 mg PGE2 gel for cervical softening and eventual induction of labour; duration of pregnancy (38-42 wk) was confirmed by ultrasonic records. Global analysis revealed 48 (96%) vaginal deliveries, 43 (86%) being spontaneous labour and 5 (10%) instrumentally assisted deliveries (forceps). Caesarean section was required in 2 cases (4%). Three patients, having registered no Bishop score (above 5) progress after the first treatment, went into labour upon the second application of PGE2 gel. Mean induction-delivery time was 11 h 50 min for nulliparae and 7 h 50 min for multiparae. Mean ROM/amniotomy-delivery time was 5 h 59 min for nulliparae and 3 h 11 min for multiparae. Four neonates with initial Apgar scores below 7 registered immediately higher values after adequate reanimation manouvres.

Adolescent↗

PubMed1985