Autonomic neurocardiogenic syndrome is stonewalled by the universal definition of myocardial infarction

Myocardial infarction(MI) is defined as myocardial cell death due to prolonged myocardial ischemia. Clinically, troponin rise and/or fall have become the"defining feature of MI" according to the universal definition of MI(UD-MI).Takotsubo syndrome(TS) and TS-related disease conditions also cause troponin elevation with typical rise and/or fall pattern but through a mechanism other than coronary ischemia. By strict application of the clinical diagnostic criteria for type-1 MI, type-2 MI, type-3 MI, and MI with non-obstructive coronary arteries according to the UD-MI including the fourth one published recently, TS and most of the 26 other causes of troponin elevation mentioned in the fourth UD-MI may erroneously be classified as MI. The existing evidence argues for the case that TS by itself is not a MI. Hyper-activation of the autonomic-sympathetic nervous system including local cardiac sympathetic hyper-activation and disruption with nor-epinephrine churn and spillover is the most probable cause of TS. This autonomic neuro-cardiogenic(ANCA) mechanism results in myocardial "cramp"(stunning), the severity and duration of which depend on the degree of the sympathetic-hyperactivation and nor-epinephrine spillover. The myocardial cramp may squeeze the cytosolic free troponin pools causing mild to moderate troponin elevation in TS and TS-related disease conditions. This ANCA syndrome, which has hitherto been enveloped by the UD-MI over more than one decade, may occur in acute, recurrent, and chronic forms. In this critical review,the controversies of UD-MI, evidence for ANCA syndrome, and a hypothetical mechanism for the troponin elevation in ANCA syndrome are provided.     

Acute cardiac sympathetic disruption and left ventricular wall motion abnormality in takotsubo syndrome

Abstract

Takotsubo syndrome (TS) is characterized by a unique pattern of transient circumferential left ventricular wall motion abnormality (LVWMA). The LVWMA in TS may be localized to the apical, mid-apical, mid-ventricular, mid-basal or basal regions of the left ventricle. Focal and generialized (global) LVWMA have also been reported. In the acute phase of TS, the hyperkinetic valve-like motion of the basal segments and/or the hyperkinetic slingshot-like motion of the apical segments combined with the firm stunned a-, hypokinetic segments result in a conspicuous left ventricular ballooning during systole. The LVWMA in TS follows most probably the local cardiac sympathetic nerve distribution and caused by local cardiac sympathetic disruption and noradrenaline spillover.     

Plasma Epinephrine Level and its Causal Link to Takotsubo Syndrome Revisited: Critical Review with a Diverse Conclusion

Takotsubo syndrome (TS) is a recognized acute cardiac syndrome with a clinical presentation resembling that of an acute coronary syndrome (ACS). The defining feature of TS is the reversible left ventricular wall motion abnormality (LVWMA), which has a unique circumferential pattern resulting in a conspicuous ballooning of the left ventricle during systole, and extending beyond the coronary artery supply territory. The pathogenesis of TS is still elusive and several pathophysiological mechanisms have been proposed. A common portrayal of the syndrome in the literature is that the disease is characterized by massive surge of plasma catecholamines including epinephrine. Based on the assumption of massive plasma epinephrine elevation, some investigators hypothesized that the circulatory plasma epinephrine plays a pivotal role in the pathogenesis of TS. One typical such hypothesis is epinephrine induced switch in signal trafficking causing apical or mid-apical ballooning in TS. In-depth analysis of the literature reveals that no study with certainty has shown “massive” plasma epinephrine elevations in TS. Furthermore, the literature evidences challenging the epinephrine-induced switch in signal trafficking are substantial. In this review, sufficient data, indicating that the plasma epinephrine in TS is either normal or moderately elevated in all studies, are provided. Noteworthy, epinephrine may act as a trigger factor for TS-induction but there is no evidence for a direct causal link between epinephrine and TS.     

Bromocriptine-induced coronary spasm caused acute coronary syndrome, which triggered its own clinical twin--Takotsubo syndrome

Bromocriptine-induced coronary spasm (BICS) causing myocardial infarction has been reported. Association between BICS and Takotsubo syndrome (TS) has not been described. We report on a 37-year-old woman presenting with a clinical picture of acute coronary syndrome 1 day after initiation of treatment with bromocriptine for ablactation 3 weeks after a full-term spontaneous vaginal delivery. Coronary angiography showed diffuse narrowing of a large diagonal branch. Left ventriculography showed widespread hypokinesia extending beyond the diagonal branch supply region. There was a slight elevation of myocardial infarction biomarkers that was disproportional to the degree of left ventricular dysfunction. Follow-up coronary angiography, intravascular ultrasound and left ventriculography showed normal coronary arteries including the diagonal branch and complete normalization of the left ventricular function. Cardiac magnetic resonance examination showed no signs of late myocardial gadolinium enhancement. The clinical picture and course of the disease was consistent with TS. Consequently, we describe for the first time a case of TS triggered by myocardial ischemia caused by BICS. Furthermore, our case and sufficient supporting data from the literature demonstrate that acute coronary syndrome is an important and frequent but up till now missed trigger factor for TS.     

Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation

BACKGROUND: Power spectral analysis of heart rate variability (HRV) has been used to indicate cardiac autonomic function. High-frequency power relates to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone; however, the relationship of low-frequency (LF) power to cardiac sympathetic innervation and function has been controversial. Alternatively, LF power might reflect baroreflexive modulation of autonomic outflows. OBJECTIVE: We studied normal volunteers and chronic autonomic failure syndrome patients with and without loss of cardiac noradrenergic nerves to examine the relationships of LF power with cardiac sympathetic innervation and baroreflex function. METHODS: We compared LF power of HRV in patients with cardiac sympathetic denervation, as indicated by low myocardial concentrations of 6-[(18)F] fluorodopamine-derived radioactivity or low rates of norepinephrine entry into coronary sinus plasma (cardiac norepinephrine spillover) to values in patients with intact innervation, at baseline, during infusion of yohimbine, which increases exocytotic norepinephrine release from sympathetic nerves, or during infusion of tyramine, which increases non-exocytotic release. Baroreflex-cardiovagal slope (BRS) was calculated from the cardiac interbeat interval and systolic pressure during the Valsalva maneuver. RESULTS: LF power was unrelated to myocardial 6-[(18)F] fluorodopamine-derived radioactivity or cardiac norepinephrine spillover. In contrast, the log of LF power correlated positively with the log of BRS (r=0.72, P <0.0001). Patients with a low BRS (相似文献   

Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxyphenylglycol and norepinephrine.

BACKGROUND. Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter at neuroeffector sites but does not distinguish neuronal release or reuptake in determining this amount or provide information about other aspects of sympathetic function. This report examines how cardiac spillover of the norepinephrine metabolite dihydroxyphenylglycol (DHPG) provides additional distinct information about cardiac sympathetic function. METHODS AND RESULTS. Arterial and coronary venous blood samples were taken during cardiac catheterization and intravenous infusion of [3H]norepinephrine in 57 subjects. Subjects were given intravenous yohimbine or underwent mental stress, handgrip exercise, and cycling exercise to activate sympathetic nerves or were given intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic activation by 65% of the increase of norepinephrine. This and the desipramine-sensitive cardiac production of [3H]-labeled DHPG from [3H]norepinephrine indicated that 10.5 times more endogenous norepinephrine is recaptured than escapes into plasma; that more than 90% of recaptured norepinephrine is sequestered into storage vesicles; and that under resting conditions, most cardiac spillover of DHPG and turnover of norepinephrine are from metabolism of transmitter leaking from vesicles; the latter process is independent of exocytotic transmitter release with a rate at rest over 100-fold that of norepinephrine spillover and over 10-fold that of norepinephrine reuptake. CONCLUSIONS. Cardiac spillover of DHPG provides information about processes close to or within sympathetic nerve endings that cannot be provided by measurements of norepinephrine spillover alone. This includes quantitative information about the role of neuronal uptake in terminating the actions of norepinephrine at neuroeffector sites and the importance of vesicular-axoplasmic exchange of norepinephrine as a dynamic process contributing to norepinephrine turnover.     

Cardiac and pulmonary norepinephrine release and removal in the dog

Norepinephrine extraction and spillover rates were determined in the heart and lungs of anesthetized dogs under resting conditions, during sympathetic stimulation, and during epicardial pacing. The fractional extraction of norepinephrine across the coronary and pulmonary vascular beds was measured from the venoarterial difference in tritiated norepinephrine after infusion of a tracer dose to a steady state level. Cardiac extraction averaged 0.299 +/- 0.03 and pulmonary extraction averaged 0.215 +/- 0.014; extraction was unaffected by sympathetic stimulation or pacing. Norepinephrine spillover from sympathetic nerve terminals in the heart and lungs was measured from the venoarterial difference in endogenous norepinephrine and plasma flow after correction for the extraction component. Cardiac norepinephrine spillover increased linearly with increasing frequency of sympathetic stimulation to 7.44 times resting levels at 2 Hz. During pacing, there was no change in cardiac norepinephrine spillover despite marked changes in heart rate. Norepinephrine spillover was demonstrated under resting conditions in the lung and was greater than observed in the heart. Pulmonary norepinephrine spillover increased with sympathetic stimulation to 4.15 times resting levels at 2 Hz. It is possible to separate the contributions of norepinephrine extraction and spillover to measured venoarterial differences of norepinephrine under physiological conditions in the dog.     

Effects of nitroprusside on cardiac norepinephrine spillover and isovolumic left ventricular relaxation in the normal and failing human left ventricle

BACKGROUND: Left ventricular isovolumic relaxation responses to changes in afterload or preload may be mediated, in part, by reflex changes in sympathetic nervous system activity. PATIENTS AND METHODS: The authors examined whether changes in left ventricular isovolumic relaxation during changes in load were associated with changes in cardiac norepinephrine spillover. Six patients with normal left ventricular function and 12 patients with congestive heart failure secondary to left ventricular systolic dysfunction were studied. Measurements of left ventricular isovolumic relaxation (Tau) were obtained using a high fidelity left ventricular pressure manometer, before, during and after infusion of nitroprusside. Total body and cardiac norepinephrine spillover were measured using a radiotracer infusion. RESULTS: Nitroprusside caused significant reductions in systemic arterial and left ventricular end-diastolic pressures, changes that were similar in the two groups. In people with normal left ventricular systolic function, these changes were associated with significant increases in both systemic and cardiac sympathetic activity, but no change in Tau. In the group with congestive heart failure, cardiac norepinephrine spillover did not change; however, there was a significant increase in the rate of left ventricular isovolumic relaxation. CONCLUSION: This study confirms that in the failing human left ventricular, isovolumetric relaxation is sensitive to changes in loading conditions induced by the nitrosovasodilator nitroprusside. Importantly, this load sensitivity is not associated with reflex increases in cardiac sympathetic activity.     

Plasma norepinephrine as an indicator of sympathetic neural activity in clinical cardiology

This review summarizes the available medical literature about plasma norepinephrine, which has been used as an indicator of sympathetic neural activity in clinical cardiology. Plasma norepinephrine levels are elevated in myocardial infarction and congestive heart failure, and the norepinephrine concentration varies with severity of disease. Patients with ischemic heart disease at rest show essentially normal plasma norepinephrine, but no studies have assessed norepinephrine levels during spontaneously occurring typical angina pectoris. Plasma norepinephrine also is increased during hypertension occurring after coronary bypass surgery or repair of aortic coarctation. Propranolol increases plasma norepinephrine, and acute withdrawal of propranolol does not. Sodium restriction increases plasma norepinephrine in healthy persons, but no information is available about its effect on patients with congestive heart failure.

Insufficient data are available to make strong inferences about sympathetic activity in cardiomyopathy, essential hypertension or pulmonary hypertension, and little or no information is available about plasma norepinephrine in ventricular fibrillation without myocardial infarction, the mitral valve prolapse syndrome, digoxin effect, syndromes associated with prolonged electrocardiographic Q-T interval and the hyperkinetic heart syndrome.     

Neuronal reuptake of norepinephrine and production of dihydroxyphenylglycol by cardiac sympathetic nerves in the anesthetized dog

BACKGROUND. Reuptake of norepinephrine by cardiac sympathetic nerves before and during two levels of electrical stimulation of the left ansa subclavia was estimated in anesthetized dogs from the cardiac production of dihydroxyphenylglycol (DHPG), the intraneuronal metabolite of norepinephrine. METHODS AND RESULTS. The method depended on the effects of neuronal uptake blockade with desipramine on the cardiac production of [3H]DHPG from intravenously infused [3H]norepinephrine. The ratio of the desipramine-induced decrease in the cardiac extraction of [3H]norepinephrine to the production of [3H]DHPG was used to transform the cardiac production of DHPG from recaptured norepinephrine into a rate for norepinephrine reuptake. Cardiac spillover of norepinephrine into plasma increased from 49 +/- 12 to 205 +/- 40 and 451 +/- 118 pmol/min during sympathetic activation. Cardiac DHPG production increased from 108 +/- 18 to 166 +/- 34 and 240 +/- 47 pmol/min. Desipramine decreased resting cardiac DHPG production by 20% and completely blocked the stimulation-induced increase. Thus, most (80%) cardiac DHPG produced at rest was derived from norepinephrine leaking from storage vesicles. This amount remained constant, and that derived from recaptured norepinephrine increased during sympathetic activation. The cardiac extraction of [3H]norepinephrine (126,000 dpm/min) and production of [3H]DHPG (3,790 dpm/min) were decreased by 55-57% after desipramine. Thus, only 3% of the norepinephrine recaptured by cardiac sympathetic nerves appeared in plasma as DHPG. The remainder was sequestered into storage vesicles (more than 94%) or ultimately formed metabolites other than DHPG (less than 3%). Reuptake of norepinephrine by cardiac sympathetic nerves was 1,188 +/- 476 pmol/min and increased in parallel with cardiac norepinephrine spillover to 4,182 +/- 1,982 and 6,594 +/- 2,241 pmol/min during sympathetic stimulation. CONCLUSIONS. Of the norepinephrine released by cardiac sympathetic nerves, 16-fold more was recaptured than entered plasma. Combined estimation of norepinephrine reuptake and spillover offers an approach to assess the efficiency of neuronal reuptake in disorders of cardiac function.     

Catecholamine release in coronary sinus during vasospastic angina induced by ergonovine

In seven patients with spontaneous angina and three control subjects, aortic and coronary sinus norepinephrine and epinephrine were assessed. Samples were taken in basal conditions and during ergonovine test in coronary sinus and aorta. The behaviour of some hemodynamic parameters as heart rate, blood pressure, left ventricular end diastolic pressure and coronary sinus flow was also studied. Resting myocardial norepinephrine and epinephrine flux was similar for both groups. In ischemic patients ergonovine induced a coronary spasm accompanied by an evident reduction of coronary sinus flow and a slight increase in arterial epinephrine and norepinephrine concentrations. However, a significant decrease in the net myocardial norepinephrine and epinephrine release was evidenced. After ergonovine, not significant changes in norepinephrine and epinephrine concentration and release resulted in control subjects. The increase in peripheral catecholamine concentrations found in ischemic patients during ergonovine test could represent a reflex activation of sympathetic activity induced by an ischemia dependent ventricular mechanical disfunction. The decrease in myocardial catecholamine release during angina could be justified by sequestration of epinephrine and norepinephrine in ischemic areas induced by vasospasm or reflex inhibition of cardiac sympathetic tone.     

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

BACKGROUND: Erectile dysfunction is common in patients with chronic heart failure and sildenafil is an effective treatment option in this population. Sildenafil has been reported to increase sympathetic outflow in normal volunteers. To date, experience with sildenafil in patients with congestive heart failure is limited and the impact of phosphodiesterase-5 inhibition on sympathetic activity in this population has not been evaluated. METHODS AND RESULTS: 10 patients with heart failure (ejection fraction 23+/-3%) were studied. Generalized and cardiac sympathetic activity responses to an intravenous infusion of sildenafil were measured by the norepinephrine spillover method. In response to sildenafil, there was a significant reduction in mean pulmonary artery (-26+/-5%, P<0.01) and mean arterial pressures (-8+/-1%, P<0.01). These hemodynamic responses were accompanied by a 22+/-5% reduction in cardiac norepinephrine spillover (P<0.02) but no change in total body norepinephrine spillover. CONCLUSIONS: The acute administration of sildenafil is associated with a modest reduction in systemic arterial blood pressure and a more substantial reduction in pulmonary arterial pressure. These hemodynamic changes are observed in the absence of systemic sympathetic activation and are associated with a reduction in cardiac norepinephrine spillover in patients with chronic heart failure. These observations are relevant given the high prevalence of erectile dysfunction in this patient population.     

Exogenous angiotensin II does not facilitate norepinephrine release in the heart

Studies on the effect of angiotensin II on norepinephrine release from sympathetic nerve terminals through stimulation of presynaptic angiotensin II type 1 receptors are equivocal. Furthermore, evidence that angiotensin II activates the cardiac sympathetic nervous system in vivo is scarce or indirect. In the intact porcine heart, we investigated whether angiotensin II increases norepinephrine concentrations in the myocardial interstitial fluid (NE(MIF)) under basal conditions and during sympathetic activation and whether it enhances exocytotic and nonexocytotic ischemia-induced norepinephrine release. In 27 anesthetized pigs, NE(MIF) was measured in the left ventricular myocardium using the microdialysis technique. Local infusion of angiotensin II into the left anterior descending coronary artery (LAD) at consecutive rates of 0.05, 0.5, and 5 ng/kg per minute did not affect NE(MIF), LAD flow, left ventricular dP/dt(max), and arterial pressure despite large increments in coronary arterial and venous angiotensin II concentrations. In the presence of neuronal reuptake inhibition and alpha-adrenergic receptor blockade, left stellate ganglion stimulation increased NE(MIF) from 2.7+/-0.3 to 7.3+/-1.2 before, and from 2.3+/-0.4 to 6.9+/-1.3 nmol/L during, infusion of 0.5 ng/kg per minute angiotensin II. Sixty minutes of 70% LAD flow reduction caused a progressive increase in NE(MIF) from 0.9+/-0.1 to 16+/-6 nmol/L, which was not enhanced by concomitant infusion of 0.5 ng/kg per minute angiotensin II. In conclusion, we did not observe any facilitation of cardiac norepinephrine release by angiotensin II under basal conditions and during either physiological (ganglion stimulation) or pathophysiological (acute ischemia) sympathetic activation. Hence, angiotensin II is not a local mediator of cardiac sympathetic activity in the in vivo porcine heart.     

Takotsubo cardiomyopathy presenting as multivessel coronary spasm syndrome: case report and review of the literature

Takotsubo' cardiomyopathy, more recently called transient left ventricular apical ballooning syndrome, is a recently described acute cardiac syndrome. This increasingly reported syndrome consists of an acute onset of transient extensive akinesia of the apical and mid-portions of the left ventricle, producing ballooning of the apex in systole in the absence of significant coronary artery disease. The syndrome is accompanied by angina-like chest pain, electrocardiographic changes and minimal release of cardiac enzymes and biomarker levels, mimicking an acute myocardial infarction and is often preceded by an episode of emotional or physical stress, which may play a key role in the pathogenesis of the disorder. However, the exact mechanism still remains unknown. We describe the history of an 83-year-old man presenting to the emergency department with clinical findings of acute myocardial infarction with ST-segment elevation in the precordial leads, but emergency coronarography showed no significant obstruction. Left ventricular angiography demonstrated the typical apical ballooning. ST-segment elevation in the precordial leads on the admission ECG resolved the day after, but new anginal chest pain was accompanied by transient ST-segment elevation in the inferior leads, suggesting multivessel coronary spasm. Awareness of the existence of the syndrome is important and should be considered in the differential diagnosis of patients presenting with an acute coronary syndrome.     

Sympathetic stimulation and norepinephrine infusion modulate extracellular potassium concentration during acute myocardial ischemia.

The purpose of this study was to investigate whether sympathetic stimulation modulated the rise in extracellular K+ concentration ([K+]o) evoked by acute myocardial ischemia. In 35 alpha-chloralose-anesthetized dogs, we measured changes in [K+]o during acute myocardial ischemia in the presence and absence of sympathetic stimulation or norepinephrine infusion. A series of four 5-minute occlusions of the distal left anterior descending coronary artery (LAD) was completed in 18 dogs. Thirty minutes of reperfusion separated each LAD occlusion. Four to five K(+)-sensitive electrodes were inserted into the left ventricular midmyocardium that was perfused by the distal LAD. Lead II of the electrocardiogram, arterial pressure, and [K+]o were recorded, and the right atrium was paced at a constant cycle length. The first, second, and fourth LAD occlusions were done in the absence of sympathetic stimulation or norepinephrine infusion. The changes in [K+]o evoked by the first LAD occlusion differed (p < 0.05) from those elicited by the second and fourth occlusions. However, the changes in [K+]o during the second and fourth LAD occlusions were similar (p > 0.2) and served as controls for the responses obtained during the third occlusion. Two minutes before the third LAD occlusion, sympathetic stimulation (4 Hz) or norepinephrine infusion (0.25-0.5 micrograms/kg per minute i.v.) was begun and was continued until 2 minutes after reperfusion. We found that sympathetic stimulation and norepinephrine infusion increased (p < 0.05) myocardial blood flow in both normal and ischemic tissue. The mean response recorded by 23 K(+)-sensitive electrodes in 11 dogs showed that sympathetic stimulation increased (p < 0.001) the [K+]o at 1, 2, 3, 4, and 5 minutes after the onset of LAD occlusion compared with the second and fourth occlusions. In contrast, the mean response recorded by 20 K(+)-sensitive electrodes in seven dogs showed that norepinephrine infusion reduced (p < 0.02) the [K+]o at 4 and 5 minutes after the onset of LAD occlusion. These data show that sympathetic stimulation increased the [K+]o evoked by acute myocardial ischemia, an effect that was not mimicked by the intravenous administration of norepinephrine.     

Cardiac and whole body [3H]noradrenaline kinetics in ischaemic heart disease: contrast between unstable anginal syndromes and pacing induced ischaemia.

Radiotracer kinetics were used to evaluate the activity of the sympathetic nervous system in 10 patients who had had unstable ischaemic symptoms within the previous 12 weeks and 10 with stable angina. Patients with recent unstable angina or angina after recent acute myocardial infarction had higher basal cardiac noradrenaline spillover than patients with stable angina. This represents a selective increase in cardiac sympathetic tone because whole body noradrenaline spillover was not significantly increased in the patients with recent unstable angina. Atrial pacing in 15 patients caused angina in 13 but did not significantly alter cardiac noradrenaline spillover in either patients with stable or unstable angina. The flow of plasma in the coronary sinus increased during pacing but because cardiac noradrenaline extraction decreased cardiac noradrenaline clearance was not significantly altered. Both whole body noradrenaline spillover and clearance were modestly increased by pacing, and arterial noradrenaline concentration was unchanged. Patients with recent symptoms of unstable ischaemia had a sustained and selective increase in cardiac efferent sympathetic tone compared with patients with stable angina, and angina induced by atrial pacing did not cause important cardiac sympathetic activation.     

Cardiac and whole body [3H]noradrenaline kinetics in ischaemic heart disease: contrast between unstable anginal syndromes and pacing induced ischaemia

Radiotracer kinetics were used to evaluate the activity of the sympathetic nervous system in 10 patients who had had unstable ischaemic symptoms within the previous 12 weeks and 10 with stable angina. Patients with recent unstable angina or angina after recent acute myocardial infarction had higher basal cardiac noradrenaline spillover than patients with stable angina. This represents a selective increase in cardiac sympathetic tone because whole body noradrenaline spillover was not significantly increased in the patients with recent unstable angina. Atrial pacing in 15 patients caused angina in 13 but did not significantly alter cardiac noradrenaline spillover in either patients with stable or unstable angina. The flow of plasma in the coronary sinus increased during pacing but because cardiac noradrenaline extraction decreased cardiac noradrenaline clearance was not significantly altered. Both whole body noradrenaline spillover and clearance were modestly increased by pacing, and arterial noradrenaline concentration was unchanged. Patients with recent symptoms of unstable ischaemia had a sustained and selective increase in cardiac efferent sympathetic tone compared with patients with stable angina, and angina induced by atrial pacing did not cause important cardiac sympathetic activation.     

Comparative effects of angiotensin converting enzyme inhibition (perindopril) or diuretic therapy on cardiac hypertrophy and sympathetic activity following myocardial infarction in rats

The long-term effects of perindopril or chlorothiazide therapy were studied in rats after the induction of myocardial infarction by coronary artery ligation. Rats with infarction developed marked cardiomegaly, indicating the presence of chronic left ventricular dysfunction. The ratio of the norepinephrine metabolite, 3,4-dihydroxyphenylethylene glycol (DHPG) to norepinephrine (NE) was elevated in the right ventricle of rats with infarction, suggesting a chronic increase in cardiac sympathetic activity. Perindopril therapy commenced either immediately following infarction or 4 weeks following infarction reduced DHPG/NE ratios toward normal levels, and prevented or reversed cardiac hypertrophy. In contrast, chlorothiazide therapy significantly reduced DHPG/NE ratios but did not decrease cardiac hypertrophy. Perindopril reverses or prevents cardiac hypertrophy and chronic cardiac sympathetic hyperactivity following myocardial infarction, while chlorothiazide reduces cardiac sympathetic activity without influencing cardiomegaly.     

Angiotensin II and norepinephrine release: interaction and effects on the heart

BACKGROUND: Angiotensin (Ang) II may enhance the influence of the sympathetic nervous system at various levels by facilitating norepinephrine (NE) release. We investigated whether such an interaction is evident in the human heart and whether it has an impact on left ventricular (LV) structure. METHODS AND RESULTS: Ang I and Ang II concentrations were determined in arterial and coronary sinus (CS) plasma samples in a group of normotensive (n = 10) and hypertensive (n = 18) subjects. Total systemic and cardiac NE spillover was measured using isotope dilution methodology and LV structure by echocardiography. Arterial and CS concentrations of Ang I and Ang II were similar in both groups (Ang II CS, 5.8 +/- 4.0 versus 3.7 +/- 3.1 fmol/ml; P = not significant), as was the Ang II/Ang I ratio (CS, 0.56 +/- 0.17 versus 0.54 +/- 0.22 fmol/fmol; P = not significant). Total systemic (223 +/- 145 versus 374 +/- 149 ng/min; P < 0.05) and cardiac NE spillover (11.7 +/- 6.3 versus 19.4 +/- 10.5 ng/min; P < 0.05) were increased in hypertensive patients, as was LV mass index (LVMI) (86.7 +/- 14.7 versus 117.2 +/- 19.4 g/m; P < 0.001). LVMI correlated with cardiac NE spillover (r = 0.47; P < 0.02). No correlation was evident between CS Ang II and cardiac NE spillover (r = 0.001; P = not significant) or LVMI (r = -0.20; P = not significant). Arterial Ang II tended to correlate with total systemic NE spillover (r = 0.34; P = 0.081). When hypertensive subjects were divided into two groups with either high or low CS Ang II concentration, cardiac NE spillover and LVMI did not differ between the two groups. CONCLUSION: These findings suggest a growth-promoting effect of increased cardiac sympathetic tone on cardiomyocytes in hypertensive patients, but do not support the notion of a significant role of Ang II for norepinephrine release and LV hypertrophy in the hypertensive human heart.     

Acute myocardial infarction

Transient left ventricular apical ballooning or Takotsubo syndrome (TS) is characterized by transient left ventricular dysfunction, electrocardiographic changes that mimic acute myocardial infarction (AMI), and minimal release of myocardial enzymes, with no evidence of obstructive coronary artery disease. Although prognosis and outcome are relatively good, reported complications include intraventricular thrombi and embolic events. We report an extremely rare case of AMI complicating the early in‐hospital course of a patient with TS. © 2013 Wiley Periodicals, Inc.