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Biomedical subjects

R L Verrier

Publications and source records attributed to R L Verrier.

At least 55 records · Page 3Linked to original sources
PubMed1991

Dynamic tracking of cardiac vulnerability by complex demodulation of the T wave.

A link is found between T wave alternans and vulnerability to ventricular fibrillation, and a new approach is provided for quantification of susceptibility to malignant arrhythmias. Complex demodulation reveals that alternation of the electrocardiogram is concentrated during the first half of the T wave, coinciding with the vulnerable period of the cardiac cycle. During myocardial ischemia and reperfusion, there are marked increases in the degree of T wave alternans that parallel the established time course of changes in vulnerability. The influence of the sympathetic nervous system in arrhythmogenesis is also accurately detected. Ultimately, complex demodulation of the electrocardiogram could provide a technique for identification and management of individuals at risk for sudden cardiac death.

Animals↗
PubMed1991

Autonomic nervous system and coronary blood flow changes related to emotional activation and sleep.

Experimental models have been developed to investigate the influences of anger, fear, and sleep on coronary blood flow. Studies of anger in dogs with coronary stenosis indicate that the postarousal phase is particularly conducive to myocardial ischemia. Specifically, a delayed coronary vasoconstrictor response has been observed within 1-3 minutes after cessation of behavioral arousal. The response is prevented by bilateral stellectomy and can be elicited in anesthetized animals by electrical stimulation of the right or left stellate ganglion. The latter effect is averted by alpha-adrenergic blockade with prazosin. Although the basis for the protracted nature of the delayed vasoconstriction remains to be clarified, the current hypothesis is that the phenomenon results from a time-dependent imbalance between the vasoconstrictor effects of adrenergic input and the vasodilator influences of coronary pressure and/or cardiac metabolic activity. A behavioral model emulating the fear state has also been developed. When dogs that fail to exhibit anger are placed in a food-access confrontation protocol, the animals demonstrate a fearlike state evidenced by a cowering posture and somatic tremor. There is a distinct plasma catecholamine profile that is characterized by a predominant increase in epinephrine compared with norepinephrine. This is in contrast to the pattern observed during anger, in which a prevalent increase in norepinephrine is observed. Fear results in significant increases in heart rate, arterial blood pressure, and coronary arterial flow. Sleep is also associated with substantial alterations in coronary hemodynamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Anger↗
PubMed1990

Acute effects of carbon monoxide on cardiac electrical stability.

The objective of this project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability. To obtain a comprehensive assessment, diverse biological models were employed. These involved cardiac electrical testing in the normal and ischemic heart in anesthetized and conscious dogs. The experimental plan was designed both to examine the direct effects of carbon monoxide exposure on the myocardium and to evaluate possible indirect influences through alterations in platelet aggregability or changes in central nervous system activity in the conscious animal. Our results indicate that exposure to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, is without significant effect on ventricular electrical stability. This appears to be the case in the acutely ischemic heart as well as in the normal heart. It is important to note that the total exposure period was in the range of 90 to 124 minutes. The possibility that longer periods of exposure or exacerbation from nicotine in cigarette smoke could have a deleterious effect cannot be excluded. We also examined whether or not alterations in platelet aggregability due to carbon monoxide exposure could be a predisposing factor for cardiac arrhythmias. A model involving partial coronary artery stenosis was used to simulate the conditions under which platelet plugs could lead to myocardial ischemia and life-threatening arrhythmias. We found no changes either in the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Thus, carbon monoxide exposure does not appear to alter platelet aggregability or its effect on coronary blood flow during stenosis. In the final series of experiments, we examined the effects of carbon monoxide exposure in the conscious state. The rationale was to take into consideration possible adverse consequences mediated by the central nervous system. We found no adverse effects on cardiac excitable properties in response to either a 2-hour or 24-hour-exposure paradigm. This appears to argue against major deleterious influences of carbon monoxide exposure as a result of direct myocardial actions or indirect actions mediated through effects on central nervous system activity.

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↗
PubMed1989

Differential effects of sleep stage on coronary hemodynamic function during stenosis.

We have demonstrated in a previous study that in the normal heart REM sleep induces surges in heart rate and coronary blood flow which are abolished by bilateral stellectomy. To study the effects of sleep in the stenosed coronary circulation, dogs were instrumented with Doppler flow probes and hydraulic occluders around the left circumflex coronary artery to measure coronary blood flow and to produce a 60% flow reduction. Catheters were placed in the aorta to measure mean arterial blood pressure. Electrodes were implanted via the frontal sinus to identify sleep stages. In the absence of stenosis, mean blood pressure was 95 +/- 3 mmHg, HR was 111 +/- 4 bpm, and coronary blood flow was 33 +/- 2 ml/min. During stenosis, REM induced episodic increases in heart rate which were accompanied by 38% decreases in coronary blood flow. We conclude that in the stenosed coronary circulation, REM sleep produces episodic sinus tachycardia and coronary blood flow reduction.

Animals↗
PubMed1989

Comparative effects of the opioids fentanyl and buprenorphine on ventricular vulnerability during acute coronary artery occlusion.

Fentanyl, a mu selective opioid agonist in wide clinical use, raises the ventricular fibrillation threshold in the normal canine myocardium. We have previously shown that this effect is amplified by haemorrhagic stress. In order to determine if mu receptor activation is antifibrillatory during acute myocardial ischaemia, we compared the effects of two mu selective agents, fentanyl and buprenorphine, in open chest chloralose anaesthetised dogs. Each drug was administered intravenously in two doses 1 h apart (fentanyl 30 micrograms.kg-1.dose; buprenorphine 0.3 mg.kg-1.dose). Ventricular fibrillation threshold was measured during right ventricular pacing using the single stimulus technique. The threshold was determined before and during a 10 min left anterior descending coronary artery occlusion. Prior to fentanyl administration, ventricular fibrillation threshold decreased from a control value of 19(SEM 2) mA to 12(1) mA during coronary artery occlusion. After the first dose of this drug an attenuation in the ischaemia induced fall in fibrillation threshold from 23(4) mA to 15(2) mA was observed. After the second dose of fentanyl the decline in fibrillation threshold was significantly blunted at 22(4) mA during control and 18(3) mA during occlusion, p less than 0.05 compared to no drug. In an additional series of experiments atropine sulphate abolished the antifibrillatory action of fentanyl, indicating that vagal efferent activation is responsible for the protective effect of the drug during acute myocardial ischaemia. This is in contrast with its mode of action during haemorrhage, when it enhances vagal afferent inhibition of sympathetic tone, and atropine pretreatment is without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Differential effects of sleep stage on coronary hemodynamic function.

The sleep-wake cycle results in distinctive patterns of autonomic nervous system activity. The present study examined the effects of rapid eye movement and slow-wave sleep on coronary hemodynamic function in chronically instrumented dogs. Mean arterial blood pressure was measured via a catheter in the aorta, and coronary blood flow was determined with Doppler probes placed around the left circumflex and right coronary artery. Identification of sleep stages was accomplished by means of electrodes implanted via the frontal sinus to record electro-oculogram, electromyogram, and electroencephalogram. Results indicated that during slow-wave sleep there were moderate but significant reductions in heart rate, 9% decreases in left coronary blood flow, and increases in coronary vascular resistance. In rapid-eye-movement sleep, the circumflex coronary blood flow base line returned to awake levels, and there were pronounced, phasic 35% increases in heart rate and 35% increases in coronary blood flow lasting 15-20 s. These surges were eliminated by stellectomy, indicating that they were mediated by the sympathetic nervous system.

Animals↗
PubMed1988

Coronary distending pressure and delayed myocardial ischemia.

The role of blood pressure alterations in the delayed onset of myocardial ischemia following sympathetic stimulation was studied in seven anesthetized dogs. In the presence of coronary stenosis, stimulation of the left stellate ganglion produced significant increases in heart rate and mean aortic pressure, but not in mean coronary blood flow or intracoronary pressure. Following cessation of stimulation, heart rate and aortic pressure returned to control levels over a 1- to 2-minute period. During this time, there was a progressive coronary vasoconstriction, as indicated by a significant fall in coronary arterial flow and intracoronary pressure. When the hypertensive response to stellate stimulation was prevented by controlled exsanguination, the coronary vasoconstriction was not delayed but occurred during stimulation. In the second phase of experiments, the aorta was constricted so as to raise systemic pressure to the peak level achieved during stimulation. Elevation of systemic pressure consistently restored coronary arterial blood flow and intracoronary pressure to the control values. By contrast, induction of hypertension by restimulation of the stellate ganglion failed to reverse the delayed coronary vasoconstriction. We conclude that delayed myocardial ischemia results from the imbalance between coronary distending pressure and an alpha-adrenergically mediated vasoconstrictor activity that persists following cessation of sympathetic nervous system stimulation.

Animals↗
PubMed1988

Delayed myocardial ischemia following the cessation of sympathetic stimulation.

A phenomenon entitled "delayed myocardial ischemia" has been described, in which there is a significant degree of coronary malperfusion following the cessation of behavioral stress. The primary objective of the present study was to develop a model for the delayed ischemic response in anesthetized animals to gain insights into the underlying mechanisms. In 15 morphine and chloralose-anesthetized dogs, a moderate degree of stenosis was applied to the left circumflex coronary artery by means of a toroidal balloon occluder. The pulsed Doppler technique was used to monitor coronary flow. After baseline data were obtained, the left stellate ganglion was stimulated for 30 seconds. Heart rate increased (63%), as did systemic blood pressure (41%) and flow in the left circumflex artery (47%). These parameters rapidly returned to control levels when stimulation was terminated. Forty-five to 90 seconds later, coronary flow decreased by 65% and coronary vascular resistance increased by 45%. These hemodynamic changes were accompanied by ECG abnormalities indicative of regional myocardial ischemia. The delayed ischemic response could be prevented by pretreatment with either nifedipine (20 micrograms/kg) or prazosin (0.3 mg/kg). These data indicate that the primary mechanism for the delayed ischemic response is alpha-adrenergically mediated contraction of the smooth muscle in the coronary artery wall.

Animals↗
PubMed1988

Antifibrillatory action of the narcotic agonist fentanyl.

Morphine, an opiate alkaloid with mixed mu- and delta-agonist properties, raises the ventricular fibrillation threshold in anesthetized dogs by altering autonomic tone. To elucidate further underlying structure-activity relationships, the effect of fentanyl, a nonalkaloid, mu-selective agonist in wide clinical use, was studied. Fentanyl (30 micrograms/kg) was given intravenously to 27 chloralose-anesthetized dogs, and ventricular fibrillation threshold was measured by means of the single-stimulus technique. In the baseline state fentanyl raised the ventricular fibrillation threshold by 14%. When the dogs were subjected to hemorrhagic stress, this effect was amplified to 29% (p less than 0.0001). Bilateral cervical vagotomy abolished fentanyl's antifibrillatory effect, but neither atropine sulfate (0.4 mg/kg/hr) nor atropine methylnitrate (0.5 mg/kg/hr) did so. Fentanyl's influence on the fibrillation threshold during hemorrhage was significantly reduced by bilateral stellate ganglionectomy (p less than 0.005). It is concluded that fentanyl raises the ventricular fibrillation threshold by its known sympathoinhibitory action rather than by its vagal efferent activating effect. The facts that an intact vagus is required and that hemorrhage amplifies the effect suggest that the antifibrillatory effect of fentanyl is mediated through the afferent component of the baroreflex arc.

Animals↗
PubMed1987

Influence of beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties and serum potassium concentration in the anesthetized dog.

The influence of selective beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties was studied in 18 anesthetized dogs. Selective beta 2-adrenoceptor activation by salbutamol failed to alter myocardia excitability but significantly lowered serum potassium concentration. Excitability, refractoriness, and ventricular fibrillation threshold were also not changed after administration of 100 and 200 micrograms/kg of the selective beta 2-antagonist ICI 118,551. However, at a dose of 500 micrograms/kg, refractoriness was prolonged and ventricular fibrillation threshold increased. These changes appear to be due to blockade of beta 1-adrenoceptors rather than to membrane stabilizing effects, since in catecholamine-depleted animals even the highest dose of ICI 118,551 did not alter myocardial electrical properties. It is concluded that beta 2-adrenoceptors do not influence electrophysiologic properties of the canine myocardium.

Adrenergic beta-Agonists↗
PubMed1987

Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat.

Brain serotoninergic neurons are known to participate in cardiovascular regulation. Administration of the serotonin precursor 5-l-hydroxytryptophan in conjunction with the monamine oxidase inhibitor phenelzine and the selective peripheral l-amino acid decarboxylase inhibitor carbidopa has been shown to raise the repetitive extrasystole threshold in the canine heart. The present investigation demonstrates that this drug regimen increases the cerebrospinal fluid concentration of serotonin and its major metabolite, 5-hydroxyindoleacetic acid, by 330 and 830%, respectively. By contrast, cerebrospinal fluid concentrations of norepinephrine and its major brain metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate, and of dopamine's metabolite, 3, 4-dihydroxyphenylacetic acid, were not significantly altered. Concomitantly, the ventricular fibrillation threshold was elevated by 42% and the effective refractory period prolonged by 7%. Efferent sympathetic neural activity was suppressed in the normal heart (from 7.9 +/- 1.3 to 3.9 +/- 1.1 impulses/s). The surge in sympathetic activity associated with acute myocardial ischemia was markedly attenuated. These results indicate that enhancement of central serotoninergic neurotransmission can reduce the susceptibility to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Delayed myocardial ischemia induced by anger.

The objectives of this study were to develop a reproducible behavioral model that simulates the anger state and to characterize its influence on myocardial blood flow in both the normal and compromised coronary circulations. Fourteen mongrel dogs of both sexes were studied. The animals were instrumented for the recording of electrocardiogram, arterial blood pressure, and left circumflex coronary arterial blood flow. A critical level of coronary stenosis was achieved with an adjustable occluder placed just distal to the flow probe. Anger was induced in the instrumented animals by having another dog challenge their access to food. In the absence of coronary artery stenosis, provocation of anger increased heart rate from 107 +/- 6 to 215 +/- 15 beats/min, arterial blood pressure from 95 +/- 4 to 142 +/- 5 mm Hg, and coronary blood flow from 31 +/- 5 to 72 +/- 9 ml/min. These variables returned to the preanger levels within 2 to 4 min. Induction of anger was repeated after a critical stenosis was applied to the left circumflex coronary artery. Anger increased heart rate from 112 +/- 6 to 210 +/- 16 beats/min, arterial blood pressure from 99 +/- 3 to 142 +/- 6 mm Hg, and coronary arterial flow from 23 +/- 5 to 35 +/- 7 ml/min. Within 2 to 4 min after the bout of anger, all dogs exhibited significant reductions in coronary arterial flow (35% of baseline; p less than .001), increases in coronary vascular resistance (557% of baseline; p less than .002), and ischemic ST segment changes in leads II, III, and aVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Anger↗
PubMed1987

Mechanisms of behaviorally induced arrhythmias.

Significant progress has been made in the past few years in defining the role of behavioral stress in the precipitation of cardiac arrhythmias. This is largely attributable to the development of relevant biobehavioral models and the advent of quantitative methods for assessing myocardial electrical stability in conscious animals. Classic and instrumental aversive conditioning has been shown to decrease electrical stability even in the normal heart. During evolving myocardial ischemia or infarction, the stress states can precipitate major arrhythmias, including ventricular fibrillation. Natural emotions have also been shown to be capable of altering the propensity to fibrillation. Notably, provocation of an angerlike state has been shown to decrease the vulnerable period threshold by 40% to 50%. The poststress phase can be particularly hazardous, as suggested by the profound myocardial perfusion abnormalities that have been observed within 1 to 3 min after cessation of anger. Cryogenic blockade of the thalamic gating system or its output from the frontal cortex to the brainstem blunts significantly the profibrillatory influence of stress. This indicates that discrete pathways within the central nervous system mediate the deleterious influence of aversive states on heart rhythm. Adrenergic factors appear to constitute the major effector component. This is supported by the observation that pharmacologic or surgical sympathectomy is capable of annulling the arrhythmogenic influence of diverse types of stress. The generally deleterious influence of the adrenergic system appears to be counteracted by vagal activity. The underlying mechanism is a muscarinically mediated inhibition of norepinephrine release from sympathetic nerve endings and a blunting of the actions of the adrenergic transmitters at the receptor level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Protective effect of tiapamil against ventricular fibrillation during coronary artery occlusion.

Calcium channel antagonists differ in their effects on myocardial excitable properties. This study examines whether tiapamil (100 micrograms/kg/min intravenously) is capable of reducing the susceptibility to ventricular fibrillation (VF) during acute occlusion and reperfusion of the left anterior descending coronary artery. During occlusion, tiapamil elevated the VF threshold to 17.5 +/- 8.2 mA compared to a control of 8.6 +/- 5.9 mA (2p less than 0.01). However, no significant effect was noted upon reperfusion of the vessel. Adrenergic stimulation with norepinephrine, 0.5 microgram/kg/min, lowered the VF threshold by 32% (2p less than 0.02), and by 6% (N.S.) when tiapamil was infused concurrently. Thus, tiapamil protects the heart against VF during coronary occlusion, but not during reperfusion. This appears to be mediated in part by an antiadrenergic action of the drug.

Animals↗