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Biomedical subjects

R L Verrier

Publications and source records attributed to R L Verrier.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cardiovascular consequences of anger and other stress states.

Anger is the affective state most commonly associated with myocardial ischaemia and infarction and life-threatening arrhythmias, with at least 36,000 (2.4% of 1.5 million) heart attacks precipitated annually by anger in the United States. Fear, anxiety and bereavement are also implicated in increased vulnerability to cardiac events. The lethal cardiovascular consequences of these behavioural stress states in patients with ischaemic heart disease are attributable to activation of high-gain central neurocircuitry and the sympathetic nervous system, provoking acute sinus tachycardia, hypertension, impaired myocardial perfusion and cardiac electrical instability. The fields of epidemiology, behavioural medicine and cardiovascular physiology have generated new methodologies for studying the pathophysiology of anger and other behavioural stress states with the goal of developing means to sever the link between the anger and its life-threatening consequences.

Anger↗
PubMed1996

Life-threatening cardiovascular consequences of anger in patients with coronary heart disease.

Anger is the affective state most commonly associated with myocardial ischemia and life-threatening arrhythmias. The scope of the problem is sizeable-at least 36,000 (2.4% of 1.5 million) heart attacks are precipitated annually in the United States by anger. The lethal cardiovascular consequences in ischemic heart disease are attributable to the unique physiology of this state, which activates high-gain central neurocircuitry and the sympathetic nervous system, leading to acute sinus tachycardia, hypertension, impaired myocardial perfusion, and a high degree of cardiac electrical instability. Exciting new tools have emerged from the fields of epidemiology, behavioral medicine, and cardiovascular physiology that offer considerable promise in accelerating our understanding of the pathophysiology of anger and in developing means to sever the link between anger and its life-threatening consequences.

Anger↗
PubMed1996

Potent antifibrillatory effect of combined blockade of calcium channels and 5-HT2 receptors with nexopamil during myocardial ischemia and reperfusion in dogs: comparison to diltiazem.

The need for novel antifibrillatory therapy is underscored by clinical trials indicating that the incidence of sudden cardiac death is increased by sodium or potassium channel blockade and is only partially reduced by beta-blockade. We examined the efficacy of nexopamil, which possesses the unique combination of calcium channel and 5-HT2 receptor blockade, in preventing ventricular tachycardia (VT) and fibrillation (VF) and reducing T-wave alternans magnitude during coronary artery occlusion and abrupt reperfusion in dogs. The results were compared with L-type calcium channel blockade alone with diltiazem. The effect of nexopamil was tested during a 10-min period of left anterior descending (LAD) coronary artery occlusion and release in chloralose-anesthetized dogs. T-wave alternans magnitude was assessed by complex demodulation. The drug reduced the incidence of VT during occlusion (from 5 of 6 to 0 of 6, p < 0.03) and VT/VF during abrupt reperfusion (from 5 of 6 to 0 of 6, p < 0.03) and suppressed the T-wave alternans magnitude increase induced by occlusion (from 14.62 +/- 3.96 to 1.39 +/- 0.34 mV x ms, p < 0.01) and reperfusion (from 17.33 +/- 4.67 to 2.34 +/- 0.77 mV x ms, p < 0.01). When 30-s left stellate ganglion stimulation (10 V, 5-ms pulses, 10 Hz) was superimposed on occlusion, nexopamil reduced the VT/VF incidence (from 8 of 11 to 4 of 11, p < 0.05) and T-wave alternans magnitude (from 24.80 +/- 5.05 to 15.81 +/- 5.09 mV x ms, p < 0.05). Calcium channel blockade alone with diltiazem decreased the incidence of ventricular tachyarrhythmias (from 5 of 10 to 1 of 10, p < 0.05) and T-wave alternans magnitude (from 16.75 +/- 3.06 to 2.87 +/- 1.23 mV x ms, p < 0.05) during coronary artery occlusion. During reperfusion, diltiazem's reduction in arrhythmia incidence (from 5 of 8 to 2 of 8) was not statistically significant, although the decrease in T-wave alternans (from 28.60 +/- 3.43 to 8.27 +/- 3.73 mV x ms, p < 0.05) was significant. Therefore, nexopamil was superior to diltiazem in protecting against reperfusion-induced arrhythmias. Nexopamil's significant antifibrillatory effect during both coronary artery occlusion and abrupt reperfusion is reliably tracked by T-wave alternans magnitude. Because the major component of the protection could be reproduced by blockade of the L-type calcium channel with diltiazem, nexopamil's antiarrhythmic action appears to be due mainly to blockade of this channel. Nexopamil's antiplatelet action through blockade of 5-HT2 receptors may confer additional protection against reperfusion arrhythmias.

Animals↗
PubMed1995

Vagal modulation of epicardial coronary artery size in dogs. A two-dimensional intravascular ultrasound study.

BACKGROUND: Because the role of tonic vagus nerve activity in regulating conduit coronary artery size remains undefined, we investigated the response of epicardial coronary artery size to changes in resting vagal tone resulting from vagotomy and muscarinic receptor blockade. METHODS AND RESULTS: Using intravascular ultrasound to measure left circumflex coronary artery cross-sectional area continuously, we examined the effects of vagotomy on left circumflex cross-sectional area in nine dogs. Lumen area decreased 20% from 8.70 +/- 2.81 to 6.92 +/- 1.97 mm2 after right vagotomy, 17% to 7.19 +/- 2.80 mm2 after left vagotomy (both P < .05 versus baseline), and 38% to 5.42 +/- 2.00 mm2 after bilateral vagotomy (P < .05 versus unilateral vagotomy). Vasoconstriction occurred despite increases in heart rate and an unchanged rate-pressure product. In six additional dogs, after acetylcholine (100 micrograms/kg i.v.), lumen area increased by 18%, although heart rate, blood pressure, and rate-pressure product were unchanged. Vasodilation was prevented by prior muscarinic blockade with glycopyrrolate. With glycopyrrolate administration and heart rate control by pacing, lumen area decreased by 26% (P = .011). When stellate stimulation was performed in a third group of eight dogs with heart rate, blood pressure, and rate-pressure product controlled by a combination of pacing and exsanguination, there was no change in coronary area, thus precluding reflex sympathetic activation as a contributor to the vasoconstriction produced by vagal withdrawal. CONCLUSIONS: Vagus nerve activity maintains tonic dilation of the left circumflex coronary artery by muscarinic receptor activation. Each vagus nerve contributes approximately equally to the tonically dilated state. Vagotomy-induced vasoconstriction occurs independently of local metabolic factors and coronary distending pressure and is a result of cholinergic withdrawal rather than reflex sympathetic activation.

Acetylcholine↗
PubMed1994

Quantification of ischaemia induced vulnerability by precordial T wave alternans analysis in dog and human.

OBJECTIVE: The aim was to examine the regional specificity of T wave alternans and the value of precordial ECG monitoring for non-invasive tracking of cardiac vulnerability during acute coronary artery occlusion and reperfusion in animals and humans. METHODS: The left ventricular ECG was monitored during two acute occlusions of the left anterior descending coronary artery and subsequent reperfusion in each of 61 chloralose anaesthetised dogs, and over 150,000 beats were analysed. In subgroups of these animals, lead II and precordial lead V5 were monitored or epicardial electrograms were recorded. In seven patients, lead II and precordial leads V1-6 were monitored during angioplasty. T wave alternans magnitude was quantified by complex demodulation. The same recording equipment and analytical methods were used in the clinical and experimental studies. RESULTS: A close temporal correspondence and linear correlation was found between T wave alternans magnitude--but not ST segment depression or ventricular premature beat incidence--and the incidence of spontaneous ventricular tachycardia and fibrillation during acute coronary artery occlusion and reperfusion. Epicardial electrograms showed alternans to be regionally specific, occurring in the ischaemic but not in the normal zones, and to predict spontaneous ventricular fibrillation and ventricular tachycardia (sensitivity = 79%, specificity = 86%). A significant linear relationship (r2 = 0.86, p < 0.01) between alternans magnitude detected in V5 and the left ventricular intracavitary lead indicates that the precordial leads could be used to assess cardiac vulnerability from the body surface. Lead V5 showed greater resolution than lead II. In humans, the precordial leads overlying the ischaemic zone were superior to lead II or Frank leads for alternans detection during both the occlusion and the reperfusion phases. In both animals and humans, alternation invariably occurred during the first half of the T wave, coinciding with the vulnerable period of the cardiac cycle and suggesting an important electrophysiological link to cardiac vulnerability. CONCLUSIONS: Alternans is regionally specific and is linearly projected to the precordium. Quantification of its magnitude in the precordial ECG may provide a non-invasive means for tracking cardiac vulnerability during acute myocardial ischaemia and reperfusion in both animals and humans.

Angina Pectoris↗
PubMed1994

Electrophysiologic basis for T wave alternans as an index of vulnerability to ventricular fibrillation.

Substantial evidence indicates that T wave alternans is an intrinsic property of ischemic myocardium. The electrophysiologic basis appears to be spatial and temporal heterogeneity of repolarization resulting from changes in action potential morphology rather than in activation sequence. Ischemia-induced changes in postrepolarization refractoriness and depressed electrical restitution of action potential duration have also been implicated. The main underlying ionic basis for T wave alternans during coronary occlusion appears to be derangements in intracellular cycling of calcium. Accumulation of potassium in the extracellular space adjoining ischemic cells and disruption in electrogenic sodium-calcium exchange may also be involved. In humans, T wave alternans has been observed in Prinzmetal's and classical angina, angioplasty, and bypass graft occlusion. Under these conditions associated with acute myocardial ischemia, alternans is restricted to the ischemic zone, and alternation in action potential morphology is an underlying factor. Recently, repolarization alternans has been shown to be a statistically significant predictor of the results of electrophysiologic testing and arrhythmia-free survival in individuals with and without organic heart disease. Collectively, these observations provide a rationale for quantitation of T wave alternans magnitude for assessment of vulnerability to life-threatening ventricular arrhythmias both in response to and independent of the effects of myocardial ischemia.

Angina Pectoris, Variant↗
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↗
PubMed1993

Hypoperfusion of the myocardium relative to myocardial metabolism during delayed coronary constriction.

OBJECTIVE: The aim was to test the hypothesis that the myocardium becomes hypoperfused, relative to its metabolic demands, during the delayed coronary constriction which is observed following termination of a period of sympathetic stimulation. METHODS: This was tested by beat by beat analysis of the ratio of coronary blood flow to the product of heart rate and systolic blood pressure (HR x SBP), an index of myocardial metabolism, in acutely instrumented open chest canine preparations, before, during, and after direct electrical stimulation of the left stellate ganglion. RESULTS: Myocardial metabolism increased in response to stellate stimulation, as evidenced by increases in heart rate, aortic blood pressure, and HR x SBP. These were accompanied by increased blood flow and decreased vascular resistance in the left anterior descending coronary artery. Delayed coronary constriction, defined as the period with the lowest coronary blood flow observed after the end of the stimulation, occurred 1 to 3 min after stimulation was terminated and was characterised by recovery of heart rate, blood pressure, HR x SBP, and coronary blood flow toward control levels, while coronary vascular resistance overshot to above control levels. The ratio of coronary blood flow to HR x SBP fell progressively in the poststimulation period to significantly less (mean 0.715, range of +/- 1 SEM 0.638 to 0.800, p < 0.05) than control (1.0, by definition) in experiments performed with partial prestenosis of the left anterior descending coronary artery. In a selected subgroup of observations with a mean reduction in coronary blood flow during delayed coronary constriction comparable to that reported previously, the flow/metabolism ratio was even lower (mean 0.239, range of +/- 1 SEM 0.202 to 0.284). CONCLUSIONS: The phenomenon of delayed coronary constriction clearly involves a mismatch between myocardial supply and demand: coronary blood flow becomes inappropriately low for the prevailing level of myocardial metabolism.

Animals↗
PubMed1993

Relationship between coronary hemodynamic changes and the phasic events of rapid eye movement sleep.

Previous studies in dogs showed dramatic increases in coronary blood flow associated with episodes of sinus tachycardia during rapid eye movement (REM) sleep. The present study demonstrates that 90% of these surges in heart rate and coronary flow are concentrated during periods of phasic REM sleep and only 10% in tonic REM sleep. Intensely phasic REM was distinguished from moderately phasic REM sleep by the degree of phasic eye movement. The surges were three times more frequent during intensely phasic REM than in moderately phasic REM sleep. However, the magnitudes of heart rate (37% +/- 3%) and coronary flow (25% +/- 3%) surges were unaffected by the specific substage of REM sleep. The incidence of surge events was almost eleven times greater in epochs of phasic REM that also contained a muscle twitch than in those that did not. During REM sleep, muscle twitches accompanying surges were not associated with any additional elevations in coronary flow or myocardial demand. Our data indicate that the sinus tachycardia-associated surges in coronary flow represent integrated autonomic responses intrinsic to phasic periods of REM sleep in dogs.

Animals↗
PubMed1993

Primary coronary vasodilation associated with pauses in heart rhythm during sleep.

We observed 162 episodes of pause in heart rhythm in chronically instrumented dogs primarily during transitions from deep slow-wave sleep to other stages of sleep. These pauses lasted 1.1-8.0 s and were followed by increases in coronary blood flow (CBF) averaging 30% and ranging up to 84%. The postpause surges in CBF do not appear to be mediated by local metabolic factors because the flow surges occurred without significant changes in the heart rate x systolic blood pressure (HRxSBP) product, a standard index of cardiac metabolic activity. Enhanced vagal tone is suggested by the background of marked respiratory sinus arrhythmia, low average heart rates, and the hallmark event, the pause in heart rhythm. In a series of experiments in alpha-chloralose-anesthetized dogs, we demonstrated that direct vagus nerve stimulation can induce both the pause in heart rhythm and the postpause increase in CBF in a pattern similar to that observed during sleep. This response was markedly attenuated after pericoronary denervation. These observations provide suggestive evidence but not definitive proof that enhanced vagal activity may be involved in the increase in CBF after spontaneous pauses in heart rhythm during sleep.

Animals↗
PubMed1993

Personal computer system for tracking cardiac vulnerability by complex demodulation of the T wave.

Complex demodulation of the T wave permits tracking of susceptibility to ventricular fibrillation under the clinically relevant conditions of acute myocardial ischemia and reperfusion. To facilitate the processing and to increase the applicability of the methods, we have developed algorithms and applied mathematical transformations that can be carried out with a personal computer. The program is self-contained and menu driven and transforms the data into a three-dimensional graphic display of magnitude of alternans (mV x ms), time in the cardiac cycle, and duration of the assessment. It is suitable for investigations with diverse experimental procedures such as coronary artery occlusion and release, autonomic interventions, behavioral stress testing, and drug administration. Our methodology may be employed in clinical conditions such as postmyocardial infarction. Prinzmetal's angina, and the long QT syndrome, wherein T wave alternans has been reported in body surface leads. Ultimately, T wave alternans analysis with use of the personal computer system may help guide therapeutic interventions.

Algorithms↗
PubMed1992

Behavioral states and sudden cardiac death.

Remarkable progress has been made both experimentally and clinically in defining the influence of behavioral states on susceptibility to life-threatening arrhythmias. Biological models have been developed to emulate anger and fear and have permitted detailed study of the intermediary mechanisms involved in stress-induced ischemia and ventricular fibrillation. The studies highlight the importance of adrenergic factors and the pathological significance of the poststress state. Clinically, the role of daily stresses in inducing silent myocardial ischemia and arrhythmias has been extensively characterized, and standardized behavioral stress tests have become available. Certain sleep states have been found to provoke ischemic episodes and arrhythmias. In particular, phasic rapid eye movement (REM) sleep has been shown both in animals and humans to conduce to perfusion abnormalities and propensity to fibrillation. Episodic surges in sympathetic nervous system activity appear to be the underlying basis. These conceptual and practical advances illustrate the promise of behavioral cardiology in the diagnosis and treatment of individuals at risk for sudden cardiac death.

Anger↗