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Biomedical subjects

Hidetsugu Asanoi

Publications and source records attributed to Hidetsugu Asanoi.

At least 19 recordsLinked to original sources
PubMed2006

Effects of nocturnal oxygen therapy on outcome measures in patients with chronic heart failure and cheyne-stokes respiration.

BACKGROUND: The effects of nasal oxygen (O(2)) supply at night using conventional home oxygen therapy (HOT) equipment on quality of life (QOL) and sleep-disordered breathing (SDB) were evaluated in patients with congestive heart failure (CHF). Nasal nocturnal O(2) therapy not only stabilizes SDB but also reduces sympathetic activity, and improves exercise capacity in patients with CHF. However, the effects of oxygen on the cardiac function and QOL of heart failure patients have not been fully elucidated. METHODS AND RESULTS: Fifty-six patients with CHF (New York Heart Association class II - III, left ventricular ejection fraction (LVEF) <or=45%) and central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR) were randomly assigned to receive either nocturnal O(2) (HOT group, n=25) or usual breathing (control group, n=31) for 12 weeks. Respiration, airflow and arterial oxygen levels were monitored with determination of apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) during sleep. LV function was determined by radionuclide angiography or echocardiography. QOL was assessed by the Specific Activity Scale questionnaire. In the HOT group, nocturnal O(2) resulted in significant improvements in AHI (21.0 +/- 10.8 to 10.0+/-11.6 events/h, mean +/- SD, p<0.001), ODI (19.5 +/- 9.8 to 5.9 +/- 8.7 dips/h, p<0.001) and Specific Activity scale (4.0 +/- 1.2 to 5.0 +/- 1.5 Mets, p<0.001). LVEF also increased from baseline to the end of the study (34.7 +/- 10.4 to 38.2 +/- 13.6%, p=0.022). CONCLUSIONS: In patients with stable CHF and CSR, HOT at night improves SDB, LV function and QOL, and thus is a valuable nonpharmacological option for the treatment of patients with CHF and CSR-CSA.

Adult↗
PubMed2005

Central sympathetic inhibition augments sleep-related ultradian rhythm of parasympathetic tone in patients with chronic heart failure.

BACKGROUND: Abnormal sleep dynamics in patients with heart failure is one of the mechanisms for the relative predominance of central sympathetic outflow over parasympathetic tone. This study was designed to examine whether central sympathoinhibition could improve the sympathovagal imbalance related to rapid-eye-movement (REM)/non-REM ultradian sleep rhythm in these patients. METHODS AND RESULTS: Beat-by-beat RR intervals of overnight electrocardiogram were serially subject to power spectral analysis in 14 patients with chronic heart failure and 13 age-matched subjects with normal cardiac function. To assess autonomic sleep dynamics, the ultradian rhythm was extracted from all-night consecutive high-frequency (HF) components of heart rate variability (HRV) before and after administration of an (alpha2)-adrenergic agonist, guanfacine. Night-time HRV in heart failure was characterized by an attenuated ultradian rhythm of HF-components with a concomitant reduction in averaged HF power. Guanfacine reduced blood pressure, heart rate, and plasma norepinephrine concentrations by 7%, 8%, and 34% (p < 0.01), respectively. After guanfacine, HF power rose by 154% (p < 0.01) with a prominent augmentation of the all-night ultradian rhythm (+361%, p < 0.01). CONCLUSIONS: Central sympathoinhibition augments a sleep-related ultradian rhythm of parasympathetic tone, suggesting a potential benefit to autonomic balancing and sleep quality in patients with chronic heart failure.

Adult↗
PubMed2005

Ischemia-induced norepinephrine release, but not norepinephrine-derived free radicals, contributes to myocardial ischemia-reperfusion injury.

BACKGROUND: Norepinephrine (NE)-derived free radicals may contribute to myocyte injury after ischemia -reperfusion, so the influence of sympathetic denervation on myocardial ischemia - reperfusion injury was investigated in the present study. METHODS AND RESULTS: Cardiac sympathetic denervation was produced in Wistar rats by a solution of 10% phenol 1 week before ischemia. Atenolol (0.5 mg/kg) was intravenously administered 10 min before the coronary occlusion. The left coronary artery was occluded for 30 min and thereafter reperfused. Cardiac interstitial fluid was collected by a microdialysis probe and free radicals in dialysate were determined by electron paramagnetic resonance (EPR) spin trapping, using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. The ratio of infarct size to the ischemic area at risk (I/R) was decreased in both the phenol and atenolol groups compared with control (28.5+/-11.3, 31.8+/-10.7 vs 50.6+/-14.7%, p<0.05). During the coronary occlusion, concentrations of interstitial NE increased markedly in the control and atenolol groups, but was unchanged in the phenol group. EPR signal intensity (relative value to internal standard) was maximal at 1 h after reperfusion and was similar in the phenol and control groups (0.32+/-0.15 vs 0.45+/-0.19). CONCLUSIONS: Cardiac denervation protected myocyte against ischemia-reperfusion injury through decreasing direct NE toxicity, but not through decreasing NE-derived free radicals.

Animals↗
PubMed2005

Evaluation of fatty acid metabolism in hearts after ischemia-reperfusion injury using a dual-isotope autoradiographic approach and tissue assay for metabolites of tracer.

UNLABELLED: We investigated whether changes in myocardial uptake of fatty acid tracer after reperfusion following transient myocardial ischemia were closely related to alterations in intracellular fatty acid oxidation. METHODS: Using a fatty acid tracer of (131)I- and (125)I-labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA), the myocardial uptake and metabolites were determined by dual-tracer autoradiography and thin-layer chromatography in rats 3 or 14 d after reperfusion following 5 or 15 min of ischemia induced by coronary artery ligation. RESULTS: 9MPA metabolites processed via beta-oxidation were lower in the ischemic region (IR) than in non-IR 3 d after 5 min of ischemia, despite no reduction of tracer uptake in IR. Oxidation of 9MPA was recovered 14 d after 15 min of ischemia in association with normalization of tracer uptake in IR, whereas both uptake and oxidation of 9MPA were markedly impaired 3 d after 15 min of ischemia, accompanied by slow clearance of myocardial tracer. CONCLUSION: Normal uptake of fatty acid tracer early after reperfusion does not always imply preserved intracellular fatty acid oxidation. However, reduction of tracer uptake might reflect impaired fatty acid oxidation.

Animals↗
PubMed2005

[Heart failure and sudden death].

Sudden death in patients with heart failure (HF) is a topic of great complexity. Neurohumoral activation including adrenergic and renin-angiotensin-aldosterone system has been a suspected trigger for lethal ventricular arrhythmias and sudden deaths. Randomized clinical trials have demonstrated that angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and beta-adrenergic blockers improve survivals in patients with HF. Although prophylactic implantable cardioverter defibrillator (ICD) therapy is effective reducing mortality in patients with left ventricular (LV) systolic dysfunction, the ICD is unlikely to be appropriate for all patients with LV systolic dysfunction. In addition, the effect of routine prophylactic use of ICDs on health care costs must be carefully considered. The care of patients with LV systolic dysfunction should be individualized for each patient.

Arrhythmias, Cardiac↗
PubMed2004

Pulse-synchronous sympathetic burst power as a new index of sympathoexcitation in patients with heart failure.

The upper limit of incidence of muscle sympathetic neural bursts can lead to underestimation of sympathetic activity in patients with severe heart failure. This study aimed to evaluate the pulse-synchronous burst power of muscle sympathetic nerve activity (MSNA) as a more specific indicator that could discriminate sympathetic activity in patients with heart failure. In 54 patients with heart failure, the pulse-synchronous burst power at the mean heart rate was quantified by spectral analysis of MSNA. Thirteen patients received a central sympatholytic agent (guanfacine) for 5 days to validate the feasibility of this new index. Both burst incidence and plasma norepinephrine level showed no significant difference between patients in New York Heart Association functional class III (94 +/- 6 per 100 heartbeats and 477 +/- 219 pg/ml, respectively) and class II (79 +/- 14 per 100 heartbeats and 424 +/- 268 pg/ml, respectively). In contrast, the burst power was useful for discriminating patients in class III from those in class II (61 +/- 8% vs. 39 +/- 10%; P < 0.05). Inhibition of sympathetic nerve activity by guanfacine was more sensitively reflected by the change of burst power (-36 +/- 25%) than by that of burst incidence (-12 +/- 14%; P < 0.001). The sympathetic burst power reflects both burst frequency and amplitude independently of the absolute values and provides a sensitive new index for interindividual comparisons of sympathetic activity in patients with heart failure.

Adult↗
PubMed2004

Saturated glucose uptake capacity and impaired fatty acid oxidation in hypertensive hearts before development of heart failure.

Abnormalities in energy metabolism may play an important role in the development of hypertensive heart failure. However, the transition from compensated hypertrophy to heart failure is not fully understood in terms of energy metabolism. In Dahl salt-sensitive (DS) and salt-resistant (DR) rats, myocardial fatty acid and glucose uptake values were determined using (131)I- or (125)I-labeled 9-methylpentadecanoic acid ((131)I- or (125)I-9MPA), and [(14)C]deoxyglucose ([(14)C]DG), fatty acid beta-oxidation was identified using thin-layer chromatography, and insulin-stimulated glucose-uptake was observed using a euglycemic hyperinsulinemic glucose clamp. Six-week-old rats were fed a diet that contained 8% NaCl, which resulted in development of compensated hypertrophy in DS rats at 12 wk of age and ultimately led to heart failure by 18 wk of age. Uptake of [(14)C]DG increased markedly with age in the DS rats, whereas (131)I-9MPA uptake was marginally but significantly increased only in animals aged 12 wk. The ratio of (125)I-9MPA beta-oxidation metabolites to total uptake in the DS rats was significantly lower (P < 0.05) at 12 (37%) and 18 (34%) wk compared with at 6 (45%) wk. Insulin increased [(14)C]DG uptake more than twofold in the DS rats at 6 wk, although this increase was markedly attenuated at 12 and 18 wk (11 and 8%, respectively). Our data suggest that in a hypertrophied heart before heart failure, fatty acid oxidation is impaired and the capacity to increase glucose uptake during insulin stimulation is markedly reduced. These changes in both glucose and fatty acid metabolism that occur in association with myocardial hypertrophy may have a pathogenic role in the subsequent development of heart failure.

Animals↗
PubMed2004

Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure.

BACKGROUND: Enhanced central hypercapnic chemosensitivity is known to mediate excessive exercise ventilation and to indicate a poor prognosis in patients with chronic heart failure. The present study was designed to elucidate the role of central sympathetic activity in the enhancement of hypercapnic chemosensitivity. METHODS: Central hypercapnic chemosensitivity and plasma norepinephrine were measured in 99 patients with chronic heart failure. In 40 patients, the alpha index was derived from simultaneous analysis of R-R interval and systolic blood pressure variability. The effects of a central sympatholytic agent, guanfacine (0.25 mg/day), on hypercapnic chemosensitivity and exercise ventilatory response were studied in 20 of these patients. RESULTS: Hypercapnic chemosensitivity was enhanced in 76% of the patients and correlated significantly with plasma norepinephrine levels (r = 0.49, P < .01) at rest. There was a significant inverse relationship between central chemosensitivity and the alpha index (r = -0.41, P < .01). Guanfacine significantly reduced plasma norepinephrine levels by 29% (P < .01) and chemosensitivity by 31% (P < .01). The beneficial effect of central sympathoinhibition with guanfacine was observed specifically in patients who had enhanced chemosensitivity prior to drug administration. Similarly, the patients with excessive exercise ventilation showed a greater reduction in exercise ventilation with this agent. CONCLUSIONS: The present findings suggest that central sympathoexcitation could play an important role in the pathogenesis of enhanced hypercapnic chemosensitivity and a resultant increase in exercise ventilation in chronic heart failure.

Carbon Dioxide↗
PubMed2004

Attenuated respiratory modulation of chemoreflex-mediated sympathoexcitation in patients with chronic heart failure.

BACKGROUND: Enhanced hypercapnic chemoreflex in chronic heart failure could modulate sympathetic nerve activity in a different manner depending on the severity of heart failure. This study was designed to evaluate the dynamic aspects of sympathoexcitation caused by central hypercapnic chemoreflex in patients with chronic heart failure. METHODS AND RESULTS: In 21 patients with chronic heart failure, wavelet analysis was applied to elucidate the spectral components of muscle sympathetic nerve activity (MSNA) and instantaneous ventilation during hypercapnic chemoreceptor stimulation. Hypercapnia increased MSNA (83+/-8 versus 29+/-9 %, P<.01) and ventilation (209+/-27 versus 190+/-21%, P<.05) more in 12 symptomatic patients than in 9 asymptomatic patients. This hypercapnic chemoreflex exerted a greater influence on the sympathetic limb than on the ventilatory limb in the symptomatic patients. The wavelet analysis revealed that the within-breath sympathoinhibition in the symptomatic patients was attenuated as compared with that in the asymptomatic patients (0.33+/-0.03 vs. 0.44+/-0.04, P<.05). CONCLUSIONS: The enhanced chemoreflex sympathetic drive and relative attenuation of ventilatory sympathoinhibition could contribute to exaggerated sympathoexcitation in patients with heart failure when they are exposed to carbon dioxide during exercise or sleep apnea.

Chemoreceptor Cells↗
PubMed2004

Prolonged activation of hemostatic markers following conversion of atrial flutter to sinus rhythm.

BACKGROUND: It remains controversial whether prophylactic anticoagulation for embolism is required in patients with atrial flutter (AFL) prior to and following cardioversion as in patients with atrial fibrillation. To evaluate the potential prothrombotic state following cardioversion of AFL, concentrations of hemostatic markers were determined before and after conversion to sinus rhythm (SR). METHODS AND RESULTS: In 12 patients (mean age 68 years) with AFL who underwent transesophageal echocardiography in the plasma concentrations of markers for platelet activity (platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG)), thrombotic status (thrombin-antithrombin III complex (TAT) and prothrombin fragments 1 and 2 (F1+2)) and fibrinolytic status (D-dimer and plasmin-alpha(2)-plasmin inhibitor complex (PIC)) were determined during AFL, and 3 days and 7 days after restoration of SR. Left atrial appendage (LAA) blood flow velocity was lower immediately after than before restoration of SR (29+/-11 vs 41+/-23 cm/s, p<0.05). Three patients developed left atrial spontaneous echo contrast immediately after restoration of SR. Although the concentrations of the markers of platelet activity did not change after restoration of SR, those of TAT and PIC increased 7 days after restoration of SR as compared with during AFL (p<0.05). CONCLUSIONS: AFL patients have a potential risk for thromboembolism after restoration of SR and therefore anticoagulation might be required in selected patients.

Aged↗
PubMed2004

Discrepant recovery course of sympathetic neuronal function and beta-adrenoceptors in rat hearts after reperfusion following transient ischemia.

UNLABELLED: Cardiac sympathetic neuronal function is closely coupled with beta-adrenoceptors and adrenergic signaling. However, the recovery process of sympathetic neuronal function and beta-adrenoceptors after reperfusion following transient ischemia is not fully understood. Accordingly, this study was performed to investigate serial changes in sympathetic neuronal function and beta-adrenoceptors after transient myocardial ischemia. METHODS: The left coronary artery of male Wister rats was ligated for 15 min followed by reperfusion. A dual-tracer method of (131)I-metaiodobenzylguanidine ((131)I-MIBG) and (125)I-iodocyanopindolol ((125)I-ICYP) was used to assess cardiac sympathetic neuronal function and beta-adrenoceptor density on days 1, 3, 7, 14, and 28 after reperfusion. Myocardial norepinephrine (NE) content in ischemic regions (IR) and in remote regions (RR) and hemodynamic indices were determined. Using a membrane preparation of the rat heart after reperfusion, the maximum specific binding (B(max)) of beta-adrenoceptors was compared with (125)I-ICYP accumulation. RESULTS: The maximum value of the rate of change in left ventricular (LV) pressure (dP/dt(max)) tended to decrease on day 1 after reperfusion but recovered thereafter. Myocardial NE content was significantly reduced in IR compared with RR on day 1 (272 +/- 49 vs. 487 +/- 93 ng/g, P < 0.01), and the decrease became more severe on day 14 (36 +/- 19 vs. 489 +/- 132 ng/g, P < 0.01) and day 28 (37 +/- 14 vs. 455 +/- 216 ng/g, P < 0.01). Decrease in the IR-to-RR uptake ratio of (131)I-MIBG was modest on day 1 (0.64 +/- 0.12) and became more severe on days 7 and 14 (0.38 +/- 0.12 and 0.35 +/- 0.13, respectively). This reduction was partially restored on day 28 (0.50 +/- 0.18). In contrast, the IR-to-RR uptake ratio of (125)I-ICYP was severely decreased until day 3 (0.60 +/- 0.13 on day 1 and 0.54 +/- 0.19 on day 3) and recovered thereafter. On day 3, B(max) was significantly lower in IR than in RR (83 +/- 17 vs. 100 +/- 12 fmol/mg, P < 0.05), but the dissociation constant did not differ between the 2 regions. CONCLUSION: The recovery course of cardiac (131)I-MIBG uptake after reperfusion following transient ischemia is quite different from that of (125)I-ICYP. Simultaneous scintigraphic portrayal of beta-adrenoceptors together with (131)I-MIBG would provide useful information regarding adrenergic system signaling in patients with coronary artery disease.

3-Iodobenzylguanidine↗
PubMed2003

Long-term treatment with low-dose, but not high-dose, guanethidine improves ventricular function and survival of rats with heart failure after myocardial infarction.

OBJECTIVES: We sought to evaluate the effects of various doses of guanethidine, a sympathoinhibitory drug, on ventricular function and survival in chronic heart failure (CHF) after myocardial infarction (MI) in rats. BACKGROUND: Direct inhibition of sympathetic outflow by a sympathoinhibitory drug might be an effective approach to therapy of CHF. However, recent clinical trials suggest that excessive suppression of sympathetic activity has an adverse effect on outcome. It remains unclear whether the beneficial effects of the sympathoinhibitory drug would be modified by its dosage. METHODS: Three doses of guanethidine (low-dose [LG], 1 mg/kg/day; medium-dose, 3 mg/kg/day; high-dose, 10 mg/kg/day) were administered via an osmotic mini-pump for 4 weeks. Hemodynamics, left ventricular (LV) diameters, plasma and myocardial norepinephrine (NE) levels, and survival were determined for four weeks after MI. RESULTS: As compared with MI rats receiving vehicle, LG suppressed LV dilation (9.2 +/- 0.9 mm vs. 11.0 +/- 0.8 mm, p < 0.05) and improved LV fractional shortening (25.0 +/- 4.5% vs. 16.4 +/- 4.7%, p < 0.05) in association with a reduction of plasma NE levels (520 +/- 250 pg/ml vs. 1,000 +/- 570 pg/ml, p < 0.05), but not with a significant reduction of noninfarcted myocardial NE levels (154 +/- 71 ng/g vs. 207 +/- 71 ng/g). Low-dose guanethidine reduced 24-h (6%) and 28-day mortality (6%), as compared with untreated MI rats (36% and 52%, respectively). High-dose guanethidine also reduced 24-h mortality (12%) but increased 28-day mortality (91%), in association with a depletion of myocardial NE. Medium-dose guanethidine had no beneficial effects on LV hemodynamics or long-term survival. CONCLUSIONS: These results indicate that the dosage of the sympathoinhibitory drug might be quite important for the treatment of CHF.

Animals↗
PubMed2003

Parametric system identification of arterial baroreflex with random perturbation of blood pressure in normal subjects.

The purpose of the study was to evaluate the dynamic nature of heart rate baroreflex under closed-loop conditions. We applied pressure perturbation with a random-interval cuff inflation to parametric system identification of the baroreflex. In 10 healthy men (six young, 27 +/- 3.9 years old, and four older, 50 +/- 3.8 years old), blood pressure variations were produced by a random-interval (0.06-0.50 Hz) cuff inflation around bilateral thighs to identify characteristics of the baroreflex with an autoregressive moving average model with exogenous input. The model faithfully described the dynamic relationship between mean blood pressure and RR interval. A theoretical 1 mmHg step input of mean blood pressure caused a rapid increase in RR intervals toward the steady state within 10 s in younger subjects. In older subjects, however, the step response showed a delayed and gradual increase in RR interval over 20 s. The steady-state gain obtained from the autoregressive moving average model with exogenous input was significantly greater than that determined from the slope of the pressure-RR relationship. The conclusion was that the dynamic baroreflex gain was quantified using a parametric system identification technique and blood pressure perturbation by means of a random-interval cuff inflation. This method would potentially be of great use in helping us gain insights into a closed-loop system of complex and dynamic cardiovascular regulation in humans.

Adult↗
PubMed2003

Supersensitive response to isoproterenol in patients with marked global reduction of cardiac metaiodobenzylguanidine uptake.

It is unknown whether the non-transplanted, denervated human heart is supersensitive to beta-adrenergic agonist in terms of inotropism and chronotropism. In the present study, 36 patients with normal left ventricular (LV) wall motion were divided into 3 groups according to the cardiac metaiodobenzylguanidine (MIBG) scintigrams: group I with normal MIBG uptake, group II with regionally reduced MIBG uptake, and group III with globally reduced MIBG uptake (heart-to-mediastinum ratio <1.6). Before isoproterenol (IP) infusion, heart rate (HR), blood pressure (BP) and echocardiographic indices were similar among the groups. There was a trend toward a greater increase in HR with IP (0.01 microg x kg (-1) x min(-1)) in group III (27+/-18 beats/min) than in groups I (20+/-8) and II (17+/-8) despite the lack of a significant difference in BP reduction by IP. During IP infusion, increases in posterior wall motion amplitude and LV fractional shortening were significantly greater in group III (4.5+/-1.8 mm and 16.4+/-5.4%, respectively) than in groups I (1.5+/-2.5 mm and 8.7+/-6.4%) and II (2.6+/-1.7 mm and 8.9+/-7.9%). The present results suggest that the sympathetically denervated human heart is supersensitive to IP and the exaggerated responses may be caused, at least in part, by a postsynaptic mechanism.

3-Iodobenzylguanidine↗
PubMed2003

Left atrial appendage function and abnormal hypercoagulability in patients with atrial flutter.

STUDY OBJECTIVES: The prevalence of thromboembolism might be higher than previously recognized in patients with atrial flutter (AFL) based on findings of transesophageal echocardiography (TEE). To evaluate the potential prothrombotic state in patients with AFL, TEE findings and hemostatic markers were compared among patient groups with AFL, normal sinus rhythm (NSR) and chronic nonvalvular atrial fibrillation (AF). DESIGN AND SETTINGS: Cross-sectional study at a university hospital. METHODS: In 28 patients (mean age, 63 years) with AFL, 58 patients (mean age, 66 years) with AF, and 27 patients (mean age, 61 years) with NSR who underwent TEE, plasma levels of markers for platelet activity (platelet factor 4 and beta-thromboglobulin [beta-TG]), thrombotic status (thrombin-antithrombin III complex and prothrombin fragments 1 and 2) and fibrinolytic status (d-dimer and plasmin-alpha(2)-plasmin inhibitor complex) were determined. RESULTS: Left atrial appendage (LAA) blood flow velocity in patients with AFL was higher (p < 0.05) than that in patients with AF, but was lower (p < 0.05) than that in patients with NSR (AF, 25 +/- 2; AFL, 44 +/- 4; NSR, 60 +/- 4 cm/s). Dense left atrial spontaneous echo contrast (SEC) was found in 4 patients (14%) with AFL and 16 patients (28%) with AF. There was no significant difference in plasma levels of hemostatic markers between the AFL group and the NSR group. AFL patients with impaired LAA function (LAA flow < 30cm/s, dense SEC, or both), however, showed higher level of d-dimer and beta-TG than those without impaired LAA function (d-dimer, 1.9 +/- 0.6 microg/mL vs 0.4 +/- 0.1 microg/mL; beta-TG, 73 +/- 17 ng/mL vs 33 +/- 5 ng/mL, p < 0.05). CONCLUSIONS: Patients with AFL as a whole are not in the prothrombotic state as compared with those with AF. However, patients with AFL and impaired LAA function are at potentially high risk for thromboembolism and might require anticoagulation.

Aged↗
PubMed2003

[Positive inotropic agents].

Despite wide prevalence of beta-blockers and angiotensin-converting enzyme inhibitors for chronic heart failure, their therapeutic efficacy remains limited because effects of these drugs depend largely on pathophysiology of an individual patient. Especially, positive inotropic therapy could be deleterious for some patients, whereas effective in improving symptoms for some patients. Recent clinical experience has led to a concept that in order to be clinically beneficial and safe, positive inotropic agents should only enhance myocardial contractility to a very modest degree in moderately to severely symptomatic patients. Positive inotropic agents could eventually serve as an individualized therapeutic option in effective management of chronic heart failure.

Acute Disease↗
PubMed2002

Cardiac sympathetic denervation modulates the sympathoexcitatory response to acute myocardial ischemia.

OBJECTIVES: This study was designed to elucidate the influence of cardiac sympathetic denervation on the sympathoexcitatory response to acute myocardial ischemia during balloon coronary occlusion (BCO) in humans. BACKGROUND: Alterations of cardiac sympathetic nerve function could modulate sympathetic reflexes originating from the ischemic area. METHODS: In 23 patients with angina pectoris, we quantified the baseline cardiac sympathetic denervation of the ischemia-related area by iodine-123 metaiodobenzylguanidine ((123)I-MIBG), and transient changes in sympathetic activity during BCO by wavelet analysis of RR interval variability. RESULTS: Balloon coronary occlusion resulted in a transient augmentation of low-frequency (LF: 0.04 to 0.14 Hz) spectral components of RR interval variability in 4 of 12 patients with cardiac denervation and in 8 of 11 patients without denervation (p < 0.01 by the chi-square test). Consequently, the increase in LF components was significantly less during BCO in patients with cardiac denervation (34%) than in those without denervation (273%) (interaction: p < 0.05). In seven patients with severe ischemia provoked by a fall of > or = 10% in the left ventricular ejection fraction, LF components increased by 506% during BCO, regardless of the condition of cardiac denervation. In contrast, in patients with mild ischemia provoked by a fall of <10% in the ejection fraction, changes of LF components during BCO were significantly less in patients with denervation than in those without denervation (84 vs. 344%, p < 0.05). CONCLUSIONS: These findings suggest that if the provoked ischemia is not severe, cardiac sympathetic denervation could prevent ischemia-induced sympathoexcitation.

3-Iodobenzylguanidine↗