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Biomedical subjects

B F Hoffman

Publications and source records attributed to B F Hoffman.

At least 19 recordsLinked to original sources
PubMed1997

Electrophysiologic effects of interactions between activated canine neutrophils and cardiac myocytes.

INTRODUCTION: Myocardial ischemia causes neutrophils to bind to activated myocytes and liberate platelet-activating factor (PAF). PAF causes delayed repolarization, early afterdepolarizations (EADs), and arrest of repolarization. We studied the effect of activation of neutrophils bound to canine cardiac myocytes to determine if such activation causes PAF generation and similar changes in transmembrane potentials. METHODS AND RESULTS: Myocytes from canine left ventricle and neutrophils from the same dog were superfused with Tyrode's solution and transmembrane potentials recorded from the former. Neutrophils (100 microL, 10(6)/mL) were added and allowed to bind to the myocytes. Neutrophils were activated with 1% zymosan-activated serum (ZAS). CV-6209 (100 nM) was used to block receptors for PAF. Liberation of PAF by activated neutrophils was quantified with a commercial radioimmunoassay kit. Neutrophils activated with ZAS caused changes in myocyte transmembrane potentials like those induced by PAF: action potential prolongation, runs of EAD, and periods of plateau arrest. PAF receptor blockade prevented neutrophil activation from altering transmembrane potentials. Neutrophils activated with 1% ZAS liberated significant amounts of PAF. CONCLUSIONS: When neutrophils bound to cardiac myocytes are activated by exposure to 1% ZAS, they cause prompt and consistent changes in myocyte electrical activity that could be arrhythmogenic for the in situ heart. These changes are similar to those caused by PAF in pharmacologic studies. Neutrophils activated in this manner generate PAF, and the effects of their activation are prevented by blockade of PAF receptors. We conclude that, during reperfusion of ischemic myocardium, PAF generated by activated neutrophils most likely is a cause of some arrhythmias.

Action Potentials↗
PubMed1997

Courts and torts: the psychiatrist preparing for trial.

OBJECTIVE: To outline how a psychiatric expert can do an impartial assessment and medicolegal report and then give an effective presentation in court that can sustain cross-examination. METHODS: The legal principles of litigating emotional trauma are reviewed, including proving causation, characterizing emotional suffering, assessing disability, and determining a realistic prognosis. RESULTS: Psychiatrists must understand the interplay of legal and psychiatric principles when they are asked to assess litigants who are suing for monetary compensation for a widening range of emotional injuries resulting from motor vehicle accidents, slips and falls, incest and sexual abuse of children, discrimination, unlawful dismissal, malpractice, human-made disasters, product liability, and intentional torts, to name a few. CONCLUSION: The psychiatrist can prepare his or her attitude, knowledge, and skills to give a presentation in court that will be credible, trustworthy, and dynamic. With adequate preparation, the psychiatric expert can bring an informed psychiatric perspective to the court that will have a significant impact on the outcome of the judicial deliberations.

Affective Symptoms↗
PubMed1997

Advance directives: principles, problems, and solutions for physicians.

Given the passage of recent legislation, the appearance of common-law reports in Canada and the United States, and the practical problems of implementation of advance directives in health care, physicians should understand the principles and issues involved. In this article, the advantages, disadvantages, and practical solutions to the problems are explored. Family physicians, geriatricians, neurologists, and psychiatrists are most likely to be consulted about advance directives in health care.

Advance Directives↗
PubMed1996

Arrhythmias caused by platelet activating factor.

INTRODUCTION: Both ischemia and reperfusion are associated with ventricular arrhythmias. In both instances, neutrophils migrate into the ischemic zone, are activated by locally released factors, and bind to myocytes. The activated neutrophils liberate platelet activating factor (PAF). We have studied the arrhythmogenic actions of PAF on transmembrane potentials of isolated canine cardiac myocytes. METHODS AND RESULTS: Cardiac myocytes were prepared from normal canine hearts by standard methods and studied in vitro by recording transmembrane potentials under control conditions and during exposure to graded doses of PAF, usually 0.25 to 1.25 micrograms (0.25 to 1.2 microM). Myocytes were superfused with Tyrode's solution (2.0 mL/min), paced at a cycle length of 1000 msec, and maintained at a temperature between 36 degrees and 38 degrees C. PAF caused a consistent and dose-dependent set of alterations in the transmembrane potential, including increased action potential duration, runs of early afterdepolarizations (EADs), and transient arrest of repolarization (PA). In addition, in some myocytes PAF caused intermittent small depolarizations both at the plateau voltage and resting potential. The effects of PAF were transient: only some residual action potential prolongation was noted after Tyrode's washout for 5 minutes. Effects of PAF were blocked in a dose-dependent manner by the PAF receptor antagonist, CV-6209. Both tetrodotoxin (1.2 x 10(-6) M) and xylocaine (5 x 10(-5) M) antagonized the ability of PAF to cause EADs and PA. CONCLUSIONS: PAF consistently exerts arrhythmogenic effects on the membrane of ventricular myocytes. Since PAF is liberated by activated neutrophils and since activated neutrophils migrate into ischemic myocardium on reperfusion, we judge that PAF liberated by such neutrophils is an important arrhythmogenic factor for reperfusion arrhythmias. The same mechanism may be a cause of arrhythmias during the evolution of infarction.

Animals↗
PubMed1995

Looking at legislative and judicial views of psychic trauma--fluctuating recognition and discrimination.

OBJECTIVE: To describe how Canadian courts and legislation have viewed psychic or emotional trauma in the past century and the principles that are used. METHODS: The author reviews major trends in legislation and judicial findings pertaining to emotional trauma and gives examples of the fluctuating and ambivalent recognition by the courts. RESULTS: The courts have progressed from refusing to acknowledge emotional trauma, to accepting emotional trauma when accompanied by physical trauma, and finally acknowledging emotional trauma even in the absence of physical injury and the "indirect" emotional trauma suffered by the relatives of victims. However, from time to time, the courts or legislation may appear to deny the distress, dysfunction or the rights of a person who suffers significant emotional symptoms after an injury. This occurred recently in Ontario where injured persons in motor vehicle accidents who suffered emotional trauma were not allowed to sue for compensation from June 1990 to January 1994. Combined efforts by a coalition of mental health professionals with victims of trauma at least partially reversed the discriminatory laws. CONCLUSIONS: Psychiatrists must continue to play a vital role in the education of the courts, politicians and the public about the realities of emotional trauma and mental illness and their long-term impact so that fair compensation can be assessed by the courts and discriminatory legislation reversed.

Canada↗
PubMed1994

Reversibility of electrophysiological abnormalities in subacute ischemia.

Twenty-four hours after occlusion of the left anterior descending coronary artery in the dog, ventricular tachycardia is the predominant rhythm. At this time, records of transmembrane potentials from the subendocardial Purkinje fibers adjacent to the infarct show a low maximum diastolic potential, prominent phase 4 depolarization, and slow response action potentials. Exposure of the fibers to pinacidil, 25-100 microM, increases resting potential to the estimated value of EK, abolishes the phase 4 depolarization, and restores action potential amplitude and Vmax toward normal. Perfusion of the bed of the occluded coronary artery with Tyrode's solution prior to isolation of the subendocardial tissues results in similar normalization of transmembrane potentials. These findings indicate: (a) that the major cause of the abnormal transmembrane potentials of the subendocardial tissues is the loss of resting potential; and (b) that abnormalities of the transmembrane potentials are caused by some substance that can be washed out by perfusion and not by a direct effect of ischemia.

Action Potentials↗
PubMed1994

Reversibility of electrophysiologic abnormalities of subendocardial Purkinje fibers induced by ischemia.

INTRODUCTION: During the subacute phase of infarction in the canine heart, the subendocardial Purkinje fibers subtended by the infarct show depolarization greater than can be accounted for by the decrease in [K+]i, and generate abnormal action potentials and spontaneous rhythms due to abnormal automaticity. We have used pinacidil to hyperpolarize these fibers and evaluate the extent to which an increase in resting potential can normalize action potential generation. METHODS AND RESULTS: Twenty-four hours after two-stage ligation of the canine left anterior descending coronary artery, preparations of subendocardial Purkinje fibers were studied in vitro by recording transmembrane potentials through standard microelectrodes and exposing the preparation to pinacidil and increases in [K+]o. Pinacidil increased resting potential to the estimated value of EK, abolished the abnormal automaticity, and restored action potentials of normal amplitude with normal values of Vmax. This effect often persisted after washout of pinacidil. Elevation of [K+]o from 4.0 to 20.0 mM slightly increased maximum diastolic potential, suggesting that the excess (over the change in EK) depolarization was caused by a decrease in gK1. CONCLUSION: The ventricular arrhythmias seen during the subacute stage of infarction probably are caused by abnormal automaticity. Our findings support the conclusion that this abnormal automaticity arises in partially depolarized subendocardial Purkinje fibers. This loss of resting potential is due in large part to a decrease in gK1. Restoration of resting potential to the value of EK permits the Purkinje fibers to develop essentially normal action potentials. An agent capable of reversing the partial block of IK,1 thus might be an effective drug for some types of arrhythmias.

Adenosine Triphosphate↗
PubMed1994

Calcium channel blockers modify electrophysiological effects induced by lytic granules from cytotoxic T lymphocytes in guinea pig ventricular myocytes.

Damage to myocytes by infiltrating cytotoxic lymphocytes, containing lytic granules and the pore-forming protein, perforin, thereof, probably contribute to the immunological rejection of the transplanted heart, to autoimmune diseases and possibly to congestive heart failure associated with myocarditis. In the present study we investigated whether electrophysiological and morphological changes induced in guinea pig ventricular myocytes by lytic granules extracted from cytotoxic T lymphocytes, are modified by L-type Ca++ channel blockers. The organic blockers, verapamil (2 microM) and nisoldipine (500 microM) were unable to prevent or inhibit any of the deleterious effects of lytic granule on action potential and myocyte morphology, and the granule-induced increase in the membrane current measured at the end of 300-msec clamp pulse. In contrast, the inorganic blockers CoCl2 (3 mM) and NiCl2 (4 mM) provided considerable protection against the granule actions mentioned above, but an equally potent Ca++ blocker, CdCl2 (3 mM) was ineffective. The protective efficacy of CoCl2 (and probably that of NiCl2) was most likely due to its capacity to reduce or block the generation by lytic granules/perforin of large-conductance (approximately 1400 pS) channels responsible for inducing Ca++ overload and cell destruction. We consider these studies of importance because they direct further studies aimed at developing effective means for attenuating cytotoxic T lymphocyte-induced tissue damage, for example during transplant rejection or in autoimmune diseases.

Action Potentials↗
PubMed1992

Immunological rejection of heart transplant: how lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes.

We investigated the mechanism by which lytic granules extracted from cytotoxic T lymphocytes (CTL) damage guinea pig ventricular myocytes in order to determine whether their actions can be related to the overall immunological rejection of the transplanted heart. Granule-induced myocyte morphological changes and final destruction were preceded by shortening of action potential duration (APD) and reductions of the resting potential and the action potential amplitude. APD shortening was probably caused by a granule-induced increase in outward current (most likely non-specific). Ryanodine, which blocks Ca2+ release from the sarcoplasmic reticulum, did not interfere with the morphological and electrophysiological effects of lytic granules. Fura-2 imaging indicated that [Ca2+]i initially increased about 2-fold from 90.0 +/- 11.5 nM, while cell length decreased less than 5% from a mean value of 99.0 +/- 9.0 microns. A further increase in [Ca2+]i (greater than 10 fold) was associated with progressive contracture and destruction, suggesting that the structural damage inflicted by lytic granules is caused by [Ca2+]i overload. The results indicate that the cytocidal action of CTL-derived lytic granules may be involved in immunologically induced damage, even to the extent of rejection of the transplanted heart.

Action Potentials↗
PubMed1992

A study of competence to consent to treatment in a psychiatric hospital.

Sixty patients admitted to an acute treatment ward in a provincial psychiatric hospital were assessed for their competence to consent to psychiatric treatment. A semi-structured interview was used to determine whether they met none, some or all of the four necessary criteria for competence outlined in the Mental Health Act of Ontario. Only 21 of the 60 patients (37%) met all four criteria necessary for a patient to be considered competent to make their own decisions regarding psychiatric treatment. The study outlines the major difficulties in the assessment of competence to consent to psychiatric treatment. Our findings suggest that 74% of patients found incompetent using the current definition in the MHA (Ontario) would fail almost any reasonable test. The implications of these findings are discussed.

Adolescent↗
PubMed1991

The isoproterenol-induced chloride current and cardiac resting potential.

Isoproterenol can induce potentially arrhymthogenic depolarizations of the resting membrane of single guinea-pig ventricular myocytes. This effect on resting potential of single guinea-pig ventricular myocytes differs qualitatively from results obtained by others from intact cardiac muscle preparations and also differs from our experience with single dog ventricular myocytes. We performed experiments on dog and guinea-pig ventricular myocytes in an attempt to clarify the effects of isoproterenol on the resting potential of mammalian ventricular myocytes. Voltage recordings with 40-60 M omega 3 M potassium chloride filled microelectrodes revealed an isoproterenol-induced depolarization of 4.3 +/- 1.0 mV in guinea-pig but no depolarization in dog myocytes. Activation of an outwardly rectifying chloride current is responsible for the isoproterenol-induced depolarization of guinea-pig ventricular myocytes. Our whole cell patch clamp recordings consistently revealed such a current in guinea-pig cells but always failed to demonstrate an isoproterenol-induced chloride current in dog myocytes under identical conditions. In contrast to single cells, isoproterenol did not depolarize intact guinea-pig papillary muscle when potential was recorded with 40-60 M omega 3 M KCl filled electrodes. Furthermore, we saw no depolarization in single guinea-pig myocytes when recording electrodes did not contain chloride. We conclude that: (1) despite activation of a chloride current, isoproterenol does not significantly depolarize guinea-pig ventricular muscle unless the driving force for the current at the resting potential is increased by elevating [Cl]i above physiological levels, and (2) an isoproterenol-induced chloride current, although demonstrable in guinea-pig ventricular cells, is not present in healthy dog ventricular cells.

Animals↗
PubMed1991

Anatomy of the tricuspid annulus. Circumferential myofibers as the structural basis for atrial flutter in a canine model.

BACKGROUND: Little anatomic information is available on the annular myocardium. This study was conducted to determine the anatomic substrate for atrial flutter due to circus movement around the tricuspid annulus in the Y-shaped incision canine model of atrial flutter. METHODS AND RESULTS: We studied photographs of the annular myocardium serial histological sections, made in either of three different planes, and compared these with photographs of the intact and blocked gross heart specimens. We found that the annulus is the most caudal region of the atrial wall. The epicardial aspect of the annulus abuts the ventricular septum or the aortic root in the medial region; in other regions, it is covered by the fat of the coronary sulcus. Its endocardial aspect is delimited by the tricuspid leaflets inferiorly and by the pectinate muscle bundles superiorly, except in the medial region where the pectinate muscle bundles are absent. The annular myocardium is bilaminated. A continuous subepicardial circumferential lamina is the most prominent and is robust in the anterior, lateral, and posterior regions, but it attenuates to a fine muscular connection in the medial region. Myofibers of its superior border merge with the pectinate muscle bundles or are admixed in the medial region with myocardium at the base of the medial atrial wall. Its inferior border makes little contact with the annulus fibrosus about the ring; however, in the medial region, these myofibers insert into fibrous tissue superior to the septal leaflet. A discontinuous, subendocardial perpendicular lamina contains myofibers that descend from the atrium; most of these myofibers insert into the annulus fibrosus about the ring, but the lamina is absent in the anteromedial region. CONCLUSIONS: We conclude that the continuous circumferential lamina provides the anatomic substrate for circus movement of excitation in this model.

Animals↗