Biomedical subjects

R D Foreman

Publications and source records attributed to R D Foreman.

At least 55 records · Page 3Linked to original sources

PubMed1994

Alpha 1-adrenergic blockade and sudden cardiac death.

INTRODUCTION: The primary goal of the present study was to test whether selective pharmacologic blockade of alpha 1 receptors, and specifically of the subtype alpha 1a, could prevent ventricular fibrillation (VF) during acute myocardial ischemia. BACKGROUND: The development of new autonomic interventions is of clinical interest in view of the failure of traditional antiarrhythmic drugs to prevent sudden death. Experimental evidence indicates that alpha 1 receptors, and in particular the subtype alpha 1a, may be involved in the genesis of malignant arrhythmias during acute myocardial ischemia and reperfusion. Despite this evidence, questions have been raised about the actual antifibrillatory efficacy of alpha-adrenergic blockade in the acutely ischemic myocardium. The effects of prazosin and of abanoquil (UK 52,046), a highly selective alpha 1a receptor blocker, were tested and compared with propranolol in a conscious animal preparation for sudden death. METHODS AND RESULTS: Ten dogs with a 1-month-old anterior wall myocardial infarction were studied. These dogs had all developed, in control conditions, VF during a 2-minute occlusion of the circumflex coronary artery while exercising (n = 9) or lying on the table (n = 1). Afterwards, the dogs underwent additional tests with the following intravenously administered drugs: abanoquil (n = 10; 1 micrograms/kg), prazosin (n = 9; 0.1 mg/kg), and propranolol (n = 10; 1 mg/kg). Internal control analysis was used. All dogs tested had recurrence of VF with both alpha-adrenergic blockers. Propranolol significantly reduced heart rate during ischemia and prevented VF in 5 of 10 dogs tested (P < 0.05). When heart rate was kept constant by atrial pacing (n = 3), 2 of the 3 animals remained protected by propranolol. Just prior to onset of VF, heart rate was not significantly different in the control and in the abanoquil tests (237 +/- 45 and 253 +/- 34 beats/min, respectively), whereas it was higher (P < 0.05) with prazosin (288 +/- 40 beats/min). CONCLUSIONS: Alpha 1 and alpha 1a receptor blockers do not prevent VF secondary to acute myocardial ischemia in the presence of elevated sympathetic activity and heart rate. In the same setting, beta-adrenergic blockade prevents the reflex heart rate increase due to ischemia and provides a significant protection.

Adrenergic alpha-Antagonists↗

PubMed1994

Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia.

Seven conscious dogs documented to be at high risk by the occurrence of ventricular fibrillation (VF) during acute myocardial ischemia were randomly assigned to 6 weeks of either daily exercise training or cage rest followed by exercise training. After 6 weeks of daily treadmill training, heart rate variability, a marker of vagal tone, increased by 74% (P < .001); baroreflex sensitivity, a marker of the capability to reflexly augment vagal activity, increased by 69% (P < .01); the repetitive extrasystole threshold, a marker of ventricular electrical stability, increased by 44% (P < .05). After exercise training, the incidence of ventricular fibrillation during acute myocardial ischemia decreased by 100%, as all animals survived. Neither passage of time nor heart rate level during ischemia contributed to the outcome. The most likely mechanism to explain the striking change in risk status is the shift in autonomic balance characterized by increased cardiac vagal activity, which was previously shown to have an antifibrillatory effect. These results suggest that exercise training in healthy individuals may decrease their likelihood of developing lethal arrhythmias during acute myocardial ischemia.

Acute Disease↗

PubMed1994

Unexpected interaction between beta-adrenergic blockade and heart rate variability before and after myocardial infarction. A longitudinal study in dogs at high and low risk for sudden death.

BACKGROUND: Heart rate (HR) variability is a marker of tonic cardiac autonomic activity and contributes in assessing risk for sudden death after myocardial infarction. Recent clinical observations have indicated that attenuation of HR variability, which occurs after myocardial infarction, may be transient. This study addresses the issue of whether autonomic control of heart rate recovers at different rates after myocardial infarction in subjects at high and low risk for ventricular fibrillation (VF). METHODS AND RESULTS: Thirty dogs, 22 with myocardial infarction and 8 sham-prepared animals, completed the study. Changes and recovery in cardiac autonomic activity after myocardial infarction were examined by measuring HR variability before and at defined intervals during the first 30 days after infarction. Each HR variability measurement was made before and after beta-blockade in dogs at high (n = 10) and low (n = 12) risk for VF. Arrhythmia risk was determined on the basis of development of VF during exercise and transient myocardial ischemia 30 days after infarction. No sham-prepared animals developed VF. Preinfarction measurements of HR variability were not different between the groups before beta-blockade, but HR variability increased much more in response to beta-blockade in animals destined to be resistant compared with susceptible animals (289 +/- 26 to 369 +/- 35 msec, delta 27.7%, versus 270 +/- 36 to 283 +/- 34 milliseconds, delta 4.8%, respectively, P < .01). Immediately after infarction, HR variability was significantly attenuated in all dogs, but in the resistant dogs it recovered to pre-myocardial infarction levels within 10 days. After the infarction, beta-blockade did not increase HR variability in either group of animals. Postoperative increases in HR variability from beta-blockade were preserved in the sham group. Susceptible animals were characterized by a persistent attenuation of HR variability throughout the 30 days. CONCLUSIONS: The depression in HR variability produced by myocardial infarction has a clearly different temporal recovery pattern between low- and high-risk animals. After myocardial infarction, beta-adrenergic blockade does not alter HR variability, thus preserving its predictive value. Before myocardial infarction, however, beta-blockade increases HR variability only in the animals destined to be at low risk for lethal arrhythmias after the infarction. The recovery pattern of HR variability after myocardial infarction may contribute to the early recognition of individuals at high risk for sudden death.

Animals↗

PubMed1993

A mechanism of cardiac pain suppression by spinal cord stimulation: implications for patients with angina pectoris.

Clinical reports show that electrical stimulation of the spinal cord reduces symptoms of angina pectoris, but so far have not provided evidence on the mechanisms involved. The hypothesis for this study was that inhibition of spinothalamic tract transmission may account for this result. Extracellular potentials of 28 spinothalamic tract neurons were recorded in anaesthetized monkeys, and the effects of dorsal column stimulation were determined on activity evoked by cardiac and somatic stimuli. Dorsal column stimulation reduced the number of cell potentials evoked by electrical stimulation of cardiopulmonary sympathetic afferent fibres in 11 spinothalamic tract cells tested. Activity evoked by intracardiac injection of bradykinin was decreased by dorsal column stimulation in six of seven neurons that responded to chemical stimulation of afferents. Differential effects of dorsal column stimulation were correlated to the cell responses to somatic field stimulation. Dorsal column stimulation inhibited activity in 12 of 12 neurons which were excited only by noxious pinch of somatic fields, whereas eight of 16 neurons which were excited by innocuous brushing of somatic fields were unaffected or excited. Transection of the dorsal column showed that the pathway transmitting inhibitory impulses descended from the stimulation site to the spinothalamic tract neurons examined. Results of this study are consistent with the concept that spinal cord stimulation reduces pain by decreasing the firing of spinothalamic tract cells which are activated by small fibre afferents. The paresthesias associated with nerve stimulation techniques may result from activation of spinothalamic tract cells which are excited by large fibre afferents. The clinical decision to employ spinal cord stimulation in patients with angina should balance the obvious benefit of pain relief against the risk of depriving the patient of an important warning signal while active myocardial ischaemia is in progress.

Afferent Pathways↗

PubMed1993

Pertussis toxin-induced ADP ribosylation of inhibitor G proteins alters vagal control of heart rate in vivo.

Prior studies have shown that in vivo systemic administration of pertussis toxin in conscious dogs catalyzes ADP ribosylation of Gi and G(o) proteins, which attenuates intracellular transduction of muscarinic receptor activation. We tested the hypothesis that this impairment may result in the alteration of the following indexes of cardiac vagal activity: baroreflex sensitivity and heart rate variability. Heart rates during submaximal exercise were also determined. These variables were measured in eight conscious dogs before and 72 hr after pertussis toxin administration. Pertussis toxin significantly reduced (P < 0.001) baroreflex sensitivity (from 18.7 +/- 2.6 to 6.8 +/- 1.4 ms/mmHg), the SD of the mean R-R intervals (from 176 +/- 17 to 61 +/- 7 ms), the mean R-R interval (from 742 +/- 32 to 527 +/- 29 ms), and the coefficient of variance [from 235 +/- 15 to 114 +/- 1 (x 1,000)]. The heart rate response to graded submaximal exercise after pertussis toxin was higher (P < 0.001) at each exercise level. In in vitro assay, cardiac tissue samples from pertussis toxin-treated dogs incorporated 10-fold less ADP ribose than what has been described previously. These data prove that the in vivo action of pertussis toxin on cardiac inhibitory G proteins has direct consequences on end-organ cardiac responses to vagal activity. This study quantifies the physiological consequences of pertussis toxin-induced impairment of inhibitory G proteins in conscious animals.

Adenosine Diphosphate Ribose↗

PubMed1992

Short latency excitation of upper cervical respiratory neurons by vagal stimulation in the rat.

Extracellular recordings were made from 29 respiration-phased neurons in the upper cervical spinal cord (C1-C3) in nine anesthetized rats while ipsilateral and contralateral vagi were stimulated via platinum hook electrodes. Neuronal responses to vagal stimulation were recorded using peristimulus histograms. An accumulation of spikes with an average latency of 4.0 +/- 0.8 (S.D.) ms occurred in 11 cells after ipsilateral stimulation. These results indicate that there are fibers in the vagus which oligosynaptically excite respiratory neurons in the upper cervical spinal cord.

Action Potentials↗

PubMed1992

Intracardiac phenylbiguanide causes excitation of spinal neurons by activation of cardiac sympathetic afferents.

The responses of spinothalamic, spinoreticular, and unidentified spinal neurons to intracardiac administration of phenylbiguanide, a 5-HT3 receptor agonist, were examined in anesthetized cats and monkeys. Eighteen neurons were excited, 5 were inhibited, and 12 were unresponsive to this stimulus. Results suggest that cardiac sympathetic afferents mediate the excitatory responses produced by phenylbiguanide, because bilateral cervical vagotomy failed to block these responses, and aortic injections of phenylbiguanide had little effect on cell activity.

Adrenergic Fibers↗

PubMed1992

Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension.

The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex.

Action Potentials↗

PubMed1992

Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons.

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1992

Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+

Afferent Pathways↗

PubMed1991

Inhibitory effects of phrenic afferent fibers on primate lumbosacral spinothalamic tract neurons.

Studies were conducted to determine if electrical or mechanical stimulation of phrenic afferent fibers (PHR) would inhibit the activity of lumbosacral spinothalamic tract (STT) neurons. Twelve monkeys were anesthetized, paralyzed, and artificially ventilated. Extracellular action potentials were recorded from 78 STT neurons located in L2-S3 spinal segments. Electrical stimulation of PHR reduced the activity of 65%, did not affect 33%, and excited 1% of STT neurons. Mechanical stimulation of the diaphragm reduced the activity of 63%, did not effect 34%, and excited 1% of lumbosacral STT neurons. Distention of the urinary bladder (UBD) inhibited 52%, did not affect 23%, excited 23%, and elicited a biphasic response in 1% of STT neurons. However, there was no correlation between the effect of PHR and UBD or somatic classification of the neurons. We conclude that electrical or mechanical stimulation of PHR can produce a generalized inhibition of lumbosacral STT neurons. This inhibitory effect of PHR is similar to inhibitory effects reported for a variety of other afferent systems.

Action Potentials↗

PubMed1991

Projection of nodose ganglion cells to the upper cervical spinal cord in the rat.

Afferent fibers mediating pain from myocardial ischemia classically are believed to travel in sympathetic nerves to enter the thoracic spinal cord. After sympathectomies, angina pectoris still may radiate to the neck and inferior jaw. Sensory fibers from those regions are thought to enter the central nervous system through upper spinal cord segments. We postulated that axons from nodose ganglion cells might project to cervical cord segments. The purpose of this study was to determine the density and pathway of vagal afferent innervation to the upper cervical spinal cord. Following an injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the upper cervical spinal cord, approximately 5.8% of cells in the nodose ganglion contained reaction product. Cervical vagotomy did not diminish the density of WGA-HRP labeled cells in the nodose ganglion. However, a spinal cord hemisection cranial to the injection site eliminated labeling of nodose cells. These data indicate that a portion of vagal afferent neurons project from the nodose ganglion to the upper cervical spinal cord. In addition, vagal afferent fibers reach the spinal cord via a central route rather than through dorsal root ganglia.

Animals↗

PubMed1991

Sympathetic-parasympathetic interaction and accentuated antagonism in conscious dogs.

The heart rate response to vagal stimulation and the interaction with sympathetic activity was evaluated in conscious dogs at rest and during exercise; the latter was used as a tool to physiologically elevate sympathetic activity. In 20 dogs with a healed myocardial infarction and in 7 healthy dogs a bipolar electrode was chronically implanted around the right cervical vagus. Vagal stimulation (3 ms; 2.1 +/- 0.7 mA; 2, 4, 6, 8, 10, 12 Hz) was performed while dogs stood on the treadmill (heart rate 120 +/- 25 beats/min) and while they exercised (201 +/- 17 beats/min). Gradual increases of the frequency of vagal stimulation gradually enhanced the inhibitory effect on heart rate both before and during exercise. During exercise, heart rate reduction was significantly greater than that produced at rest at any frequency of stimulation (P less than 0.001). This difference widened as the frequency of stimulation increased and the interaction with or without the presence of exercise was significant (P less than 0.02). Vagal stimulation produced similar effects in the seven dogs without myocardial infarction. These data demonstrate that the vagal-sympathetic "accentuated antagonism" described in anesthetized animals is also present in conscious dogs.

Animals↗

PubMed1991

Vagal reflexes and survival during acute myocardial ischemia in conscious dogs with healed myocardial infarction.

The role of vagal tone and reflexes in the genesis of life-threatening arrhythmias was investigated in a clinically relevant animal model for sudden cardiac death. Forty-five dogs with a healed anterior myocardial infarction in which transient myocardial ischemia during exercise did not induce malignant arrhythmias were utilized for the study. They underwent a further exercise and ischemia test in which atropine (75 micrograms/kg) was injected before coronary artery occlusion. Novel occurrence of ventricular arrhythmia, or worsening of the type of arrhythmia present in the control test, occurred in 23 of 45 dogs (51%) and ventricular fibrillation occurred in 11 of 45 (24%, P = 0.001). Analysis of heart rate response to acute ischemia in the control test indicates that these 11 animals had powerful vagal reflexes during coronary artery occlusion, compared with the 34 survivors (-32 +/- 35 vs. +2 +/- 27 beats/min, P = 0.003). This study indicates that approximately 75% of animals resistant to ventricular fibrillation are characterized by weak sympathetic reflexes in response to acute myocardial ischemia. In the remaining 25% powerful vagal reflexes counteract concomitant reflex sympathetic hyperactivity, decrease heart rate, and are essential for survival.

Acute Disease↗

PubMed1991

Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart.

1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction.

The interest for the antifibrillatory effect of vagal stimulation has been largely limited by the fact that this concept seemed restricted to acute experiments in anesthetized animals. To explore the potentially protective role of vagal stimulation in conscious animals we developed a chronically implantable device to be placed around the cervical right vagus. An anterior myocardial infarction was produced in 161 dogs; 1 month later an exercise stress test was performed on the 105 survivors. Toward the end of the test the circumflex coronary artery was occluded for 2 minutes. Fifty-nine (56%) dogs developed ventricular fibrillation and, before this test was repeated, were assigned either to a control group (n = 24) or to be instrumented with the vagal device (n = 35). Five dogs were excluded because of electrode malfunction. Compared with the heart rate level attained after 30 seconds of occlusion during exercise in the control test, vagal stimulation led to a decrease of approximately 75 beats/min (from 255 +/- 33 to 170 +/- 36 beats/min, p less than 0.001). In the control group 22 (92%) of 24 dogs developed ventricular fibrillation during the second exercise and ischemia test. By contrast, during vagal stimulation ventricular fibrillation occurred in only 3 (10%) of the 30 dogs tested and recurred in 26 (87%) during an additional exercise and ischemia test in the control condition (p less than 0.001 versus the vagal stimulation test; internal control analysis). Combined analysis of the tests performed in the control condition showed that ventricular fibrillation was reproducible in 48 (89%) of the 54 dogs tested. The protective effect of vagal stimulation was also significant in the group comparison analysis and even after exclusion of those four dogs in which ventricular fibrillation was not reproducible (92% versus 11.5%, control versus vagal stimulation, p less than 0.001). When heart rate was kept constant by atrial pacing, the vagally mediated protection was still significant (p = 0.015) as five (55%) of nine dogs survived the test. This study shows that vagal stimulation, performed shortly after the onset of an acute ischemic episode in conscious animals with a healed myocardial infarction, can effectively prevent ventricular fibrillation. This striking result seems to depend on multiple mechanisms having a synergistic action. The decrease in heart rate is an important but not always essential protective mechanism. The electrophysiological effects secondary to the vagally mediated antagonism of the sympathetic activity on the heart are likely to play a major role.

Animals↗

PubMed1990

Tocainide and mortality after myocardial infarction: a prospective study in conscious dogs.

The production of an anterior myocardial infarction as part of an experimental animal model for sudden death was burdened by a persistently elevated mortality rate (30%) despite the use of traditional antiarrhythmic drugs. Mortality was reduced when tocainide (600 mg three times daily) was empirically administered for 4 days before and 4 days after myocardial infarction. Retrospective analysis showed that mortality at 4 days after infarction was significantly lower in the tocainide-treated dogs than in the preceding large group of dogs that had not been so treated (5 [9%] of 55, versus 64 [32%] of 199, p less than 0.01). This difference was still evident 30 days after myocardial infarction (13 [24%] of 55 versus 83 [42%] of 199; p less than 0.05). This observation led to the present prospective study in 106 dogs with a similar protocol but with a randomized sequence. At 4 days after myocardial infarction, the mortality rate was 55% lower in the tocainide group than in the control group (7 [12.5%] of 56 versus 14 [28%] of 50; p less than 0.05). During the 10 days after treatment withdrawal 9 (18%) of 49 dogs in the tocainide group died compared with only 2 (5%) of 36 in the control group. This rebound in mortality produced similar survival figures in the two groups at 14 and at 30 days after infarction when mortality was 30% (17 of 56) in the tocainide group and 34% (17 of 50) in the control group. The tocainide plasma levels were 7.4 +/- 4 micrograms/ml the day before infarction and 7.2 +/- 3 micrograms/ml 3 days after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death.

Heart rate variability has been demonstrated both experimentally and clinically to be of prognostic importance in determining mortality after myocardial infarction. However, no paired studies have been reported to examine heart rate variability before and after myocardial infarction. The hypothesis was tested that low values of heart rate variability provided risk assessment both before and after myocardial infarction with use of an established canine model of sudden cardiac death. Risk for sudden death was assessed 1 month after myocardial infarction by a protocol in which exercise and myocardial ischemia were combined; dogs that developed ventricular fibrillation were classified at high risk for sudden death (susceptible) and the survivors were considered low risk (resistant). In resistant dogs, myocardial infarction did not affect any measure of heart rate variability: 1) mean RR interval, 2) standard deviation of the mean RR interval, and 3) the coefficient of variance (standard deviation/RR interval). By contrast, after myocardial infarction, susceptible dogs showed significant decrease in all measures of heart rate variability. Before myocardial infarction, no differences were seen between susceptible and resistant dogs. However, 30 days after infarction, epidemiologic analysis of the coefficient of variance showed high sensitivity and specificity (88% and 80%, respectively), predicting susceptibility. Therefore, results of analysis of 30 min of beat to beat heart period at rest 30 days after myocardial infarction are highly predictive for increased risk of sudden death.

Analysis of Variance↗