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ObjectiveThe number of elderly patients with heart failure (HF) has increased. We aimed to determine the clinical characteristics and in-hospital mortality of very elderly patients hospitalized for acute HF.Methods and resultsIn total, 403 consecutive patients (median [interquartile range] age 79 [70, 85] years [y]) who were hospitalized between September 2009 and March 2011 to a single cardiovascular centre in Kitakyushu, one of the most ageing metropolitan cities in Japan, were enrolled. The 2012 ESC guideline for acute HF was used for the diagnosis. The patients were divided into two groups: patients of age ≥ 85 y (n = 108, group 1) and those of age < 85 y (n = 295, group 2). Group 1 patients were characterized with statistical significance by a female predominance, higher prevalence of hypertension, lower prevalence of diabetes and chronic obstructive lung disease, lower estimated glomerular filtration rate (eGFR) and haemoglobin levels, and a higher left ventricular ejection fraction. In-hospital, all-cause mortality was significantly higher in group 1 patients (11.1% vs 4.4%, P< 0.05). Higher age, lower systolic blood pressure on admission, and lower eGFR were independently associated with mortality. Incidence of survival within 30 days was lower in group 1 than in group 2 patients (hazard ratio 0.31, 95% confidence interval 0.12 to 0.83, P= 0.02).ConclusionsIn an ageing metropolis of Japan, very elderly patients comprised nearly a quarter of acute HF hospitalizations and had a lower 30-day survival rate compared with less elderly patients.

Recently, there has been increasing concern about adverse health effects of exposure to desert dust events. However, the association between dust and the incidence of ischemic heart diseases is unknown. The aim of the present study was to elucidate whether Asian dust (AD), a windblown sand dust originating from mineral soil in China and Mongolia, is associated with the incidence of acute myocardial infarction (AMI).

ObjectiveRed cell distribution width (RDW) is a measure of variation in the volume of circulating erythrocytes and has recently emerged as a powerful prognostic marker in heart failure. We studied the eff ect of 5-month, home-based cardiac rehabilitation on RDW.Methods and resultsSixty-two patients (age: median 67 years, IQR 63-74) with chronic heart failure caused by reduced left ventricular systolic function were enrolled. Exercise time and physical activity levels out of the hospital were determined by a single-axial accelerometer. Baseline RDW values were: median 13.6, IQR 12.8-14.4%, with 13 patients (21.0%) showing values above the upper normal limit. RDW values were decreased significantly after training in the 13 patients with elevated baseline RDW values (P< 0.01), but not in the remaining 49 patients with normal baseline RDW values. There was a highly signifi cant correlation between baseline RDW and changes in RDW after exercise training (P= 0.0001, r2= 0.628, n = 62). The time spent for moderate (> 3 METs) exercise was: median 9.0, IQR 3.0-18.8 minutes per day.ConclusionsRelatively low intensity, home-based cardiac rehabilitation was associated with decreased RDW in heart failure patients with abnormal RDW.

Epicardial coronary stenosis causes myocardial ischemia; however, the role of coronary microvessels is poorly understood in the pathogenesis of effort angina. We have previously demonstrated that Rho-kinase pathway is substantially involved in coronary arterial hyperconstriction in patients with vasospastic angina and those with microvascular angina. In the present study, we tested our hypothesis that Rho-kinase is involved in coronary microvascular constriction in patients with effort angina. Intracoronary administration of fasudil (300 μg/min for 15 min), a specific Rho-kinase inhibitor, significantly increased oxygen saturation in coronary sinus vein from 37 ± 3% to 41 ± 3% (P< 0.05) but not in six age-matched controls (from 42 ± 3% to 43 ± 3%, P= NS). Furthermore, the fasudil treatment significantly ameliorated pacing-induced myocardial ischemia in patients with effort angina (magnitudes of symptom: 1.5 ± 0.6 to 0.6 ± 0.4, P< 0.01; ischemic ST-segment depression, 1.8 ± 0.3 to 1.0 ± 0.2 mm, P< 0.01; percent lactate production, 50 ± 17% to 0.4 ± 7%, P< 0.01) without significant hemodynamic changes. These results provide the first evidence that Rho-kinase is substantially involved in coronary microvascular dysfunction associated with myocardial ischemia in patients with effort angina, suggesting that Rho-kinase can be a novel therapeutic target in ischemic heart disease.

OBJECTIVES

Coronary flow reserve is reduced in patients with idiopathic dilated cardiomyopathy (DCM). We examined acute effects of intracoronary enalaprilat on metabolic coronary vasodilation during pacing tachycardia in patients. Coronary blood flow (Doppler guidewire) and diameter (quantitative angiography) were measured in seven patients with DCM and seven control subjects. In the DCM group, tachypacing increased coronary blood flow by 37 ± 22% from the baseline before enalaprilat and by 65 ± 22% (p < 0.01 vs. before treatment) after enalaprilat (0.5 μg/kg/min for 5 min, i.c.) at comparable double product. Pacing-induced dilation of the epicardial coronary artery also was greater after enalaprilat (p < 0.05). Effects of enalaprilat on coronary blood flow and diameter during pacing tachycardia were abolished by pretreatment with intracoronary administration of the nitric oxide (NO) synthesis inhibitor, NG-monomethyl-L-arginine. These beneficial effects of enalaprilat on large and small coronary vasodilation were not observed in control patients. Thus, intracoronary enalaprilat acutely augmented dilator responses of the large and small coronary arteries to pacing tachycardia in patients with DCM, and NO appeared to play an important role in mediating the effects of enalaprilat. These favorable effects of enalaprilat on the coronary circulation may be of clinical significance in patients with heart failure due to nonischemic DCM. Further long-term studies of the effects of angiotensin-converting enzyme inhibition on coronary vasodilation will be needed in this population.

Summary We report a case of a patient with vasovagal syncope, in whom isoproterenol infusion provoked vasovagal response without upright tilting. We subjected the patient, who had had two previous syncopal and several presyncopal episodes, to upright tilting with isoproterenol infusion. Before a control tilt was performed for 10min (80°), the patient was placed in the supine position for 5 min. The control tilt did not provoke a vasovagal response. With isoproterenol being infused at a dose of 1 µg/min, the sequence of positioning in the supine position for 5min and upright tilting for 10min was repeated. This dose of isoproterenol infusion did not provoke any vasovagal response in the patient, either in the supine or in the upright position. When the dose of isoproterenol infusion was then increased to 2 µg/min, the heart rate increased to 121/min, but then suddenly dropped to 74/min; systemic arterial pressure simultaneously fell from 148/80 to 108/80 mmHg. The patient complained of palpitation and anxiety, and showed profound cold sweating. The drop in the heart rate and the fall in blood pressure occurred when the patient was in the supine position, indicating that, unlike upright tilting with isoproterenol infusion, venous return was not decreased at the beginning of vasovagal response in this setting. This observation suggests that isoproterenol infusion, even without upright tilting, may provoke the vasovagal response in some patients.

Objectives.The aim of this study was to investigate the basal release of nitric oxide at spastic sites in patients with variant angina.

We investigated the effects of a new compound (3-methylsulfonyl-4-piperidinobenzoyl) guanidine hydrochloride (HOE 694) known to inhibit the Na+/H +exchanger in a porcine model of ischemia/reperfusion. Ischemia was induced by coronary occlusion (twice for 10 min, with a 30-min reperfusion interval) followed by a 4-h reperfusion period. Treated animals (n = 8) received HOE 694 as a bolus (7 mg/kg) 20 min before ischemia and subsequently as a continuous infusion (0.07 mg/kg) throughout the experiment. Control pigs (n = 11) received vehicle. Regional wall function (percentage of segment shortening, SS) of the treated animals was significantly improved as compared with that of controls after the 4-h reperfusion period (74.1 ± 2.5 vs. 50.9 ± 5.4, p < 0.005). Ventricular fibrillation (VF) could be prevented completely in treated pigs but occurred in 9 of 11 control animals (p < 0.001). Ultrastructural changes after ischemia and reperfusion were moderate and slightly abnormal in controls but much milder and completely recovered in the treated group, respectively. The tissue content of high-energy phosphates did not show a significant difference between groups. Inhibition of the sarcolemmal Na+/ H+antiporter with HOE 694 is antiarrhythmic and diminishes myocardial ischemic cell injury by preventing Na+ overload.

It has been shown that substance P causes endothelium-dependent vasodilation in the human coronary and forearm vessels. However, the precise mechanism whereby substance P dilates the coronary and peripheral vasculatures is unknown in humans. The aim of this study was to examine whether the vasodilator effect of substance P is mediated by nitric oxide in the human coronary and forearm vessels. Eight patients with normal coronary angiograms were studied for the measurements of coronary blood flow (intracoronary Doppler guide wire and quantitative coronary arteriography) and forearm blood flow (strain-gauge plethysmograph). Intracoronary acetylcholine (10 μg/min for 2 min) and substance P (30 and 90 ng/min for 2 min) increased coronary blood flow from the baseline value. Intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA) at 200 μmol significantly attenuated the magnitudes of increase in coronary blood flow induced by both acetylcholine (p < 0.01) and substance P (p < 0.01). Acetylcholine (4, 8, and 16 μg/min for 2 min) and substance P (0.8, 1.6, and 3.2 ng/min for 2 min) also increased forearm blood flow in a dose-dependent manner. Intraarterial L-NMMA (8 μmol/min for 5 min) decreased the magnitudes of increase in forearm blood flow induced by acetylcholine (p < 0.01). L-NMMA at the same dosage decreased the increase in forearm blood flow induced by substance P, but the magnitude of the inhibitory effect of L-NMMA on blood-flow responses to substance P was significantly smaller in the forearm than in coronary vessels. It is suggested that endothelium-derived nitric oxide contributes to substance P-induced vasodilation, and that the contribution of nitric oxide to substance P-induced vasodilation is smaller in the forearm than in coronary circulation.

Objectives. The present study aimed to determine the role of nitric oxide (NO) and angiotensin-converting enzyme (ACE) in bradykinin (BK)-induced dilation of human coronary arteries in vivo.

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Objectives: Coronary microembolisation in the pig heart induces angiogenesis in a model of sterile inflammation due to focal necrosis. We have recently shown in this model that insulin-like growth factor I (IGF-I) is involved in inflammation-linked angiogenic processes due to its enhanced transcription after 72 h of ischaemia by infiltrating monocytes in areas of microsphere-induced focal necrosis where capillary sprouting could be detected. To obtain further insights into this process we studied by means of Northern blot analysis and in situ hybridisation the gene expression of other members of the IGF family, i.e. the six IGF binding proteins (IGFBPs), the insulin receptor, and the type I IGF receptor. Methods: Myocardial injury was induced by injection of 25 µm non-radioactive microspheres into the left circumflex artery (LCx) in pigs that were killed after 3–24, 72, or 168 h of microembolisation. Tissue was collected from a non-ischaemic control area and the LCx region of the same heart for further analysis. Results: We found decreased IGFBP-5 (2.7-fold; P<0.02) mRNA concentrations after 72 h of microembolisation in ischaemic tissue versus control tissue from the same heart, preceded by a 1.9-fold elevated level of IGFBP-3 mRNA at 3–24 h (P<0.05). IGFBP-6 was increased in ischaemic tissue at all time points studied. In situ hybridisation identified myocytes as the main producers of IGFBP-3 and IGFBP-6 mRNA. The mRNA levels of IGFBP-2, IGFBP-4, the insulin receptor, and the type I IGF receptor were constitutively expressed but did not change after microembolisation. Neither in heart nor in other organs studied transcripts of IGFBP-1 could be detected. Furthermore, we demonstrated that mRNA of the other components of the IGF system was expressed in almost all porcine organs except liver. Conclusion: These results indicate a coordinate gene expression of the IGF system in microembolised porcine myocardium, compatible with a role of IGF-I, IGFBP-3, IGFBP-5, and IGFBP-6 in inflammation-linked angiogenesis and/or repair processes.

Objective: Angiogenesis in the porcine heart can be induced by myocardial ischaemia following vascular occlusions. This process is characterised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IGF) and interleukins (IL). The aim of the study was to examine gene expression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of coronary angiogenesis. Methods: Experimental ischaemia and subsequent focal necroses were induced by selective injection of 25 µm microspheres into the left circumflex artery. The hearts were excised after 3–168 h of microembolisation, and tissue was collected from a non-ischaemic control area and the circumflex region of the same heart for further analysis. Results: IGF-I was constitutively transcribed in normal porcine myocardium mainly by myocytes. Following microembolisation, IGF-I mRNA expression was significantly increased in the experimental region (1.8-fold) after 72 h and to a lesser extent after 168 h. In the ischaemic region, characterised by capillary sprouting, numerous mononuclear cells contained IGF-I mRNA. In contrast, IGF-II mRNA levels, constitutively produced by porcine myocytes, were not altered by microembolisation. IL-1, IL-1β, and IL-4 mRNA expression was undetectable in our animal model, whereas IL-6 was constitutively transcribed in normal and ischaemic heart and remained insensitive to microembolisation and focal necrosis. Conclusion: After microembolisation, increased IGF-I mRNA expression occurred by infiltrating monocytes in areas of microsphere induced focal necrosis, where capillary sprouting can be detected, suggesting that IGF-I is involved in inflammation linked angiogenic processes.

Objective: The aim was to examine whether ischaemic preconditioning can be renewed by a second cycle of brief coronary occlusions in pigs subjected to two different reperfusion intervals (1 h or 4 d). Methods: Ischaemic preconditioning was induced by a cycle of two 10 min occlusions of the left anterior descending coronary artery separated by 30 min of reperfusion. Infarction was induced with a subsequent 1 h occlusion and a 2 h reperfusion period. There were four experimental groups: in group I (n=5), a 30 min reperfusion was interposed after the preconditioning cycle prior to the sustained occlusion; in group II (n=5), this time frame was extended to 1 h; in group III (n=5), the preconditioning cycle was renewed 1 h after the first cycle; in group IV (n=5), the second cycle was performed 4 d later. Control pigs (n=5) were subjected to 1 h coronary occlusion and 2 h reperfusion without previous short occlusions. Infarct size was measured with p-nitro blue tetrazolium and was expressed as a percent of area at risk. Results: The percent of the risk region infarcted was 69.9(SEM 3.8)% for controls, 22.9(3.5)% in group I (p<0.001 v controls), 67.3(5.2)% in group II, 66.3(4.2)% in group III, and 17.9(3.9)% in group IV (p<0.001 v controls). Regional wall function measured with ultrasonic crystals deteriorated through the reperfusion intervals, indicating different underlying mechanisms for ischaemic preconditioning and myocardial stunning. Conclusions: Ischaemic preconditioning with two 10 min occlusions reduced infarct size resulting from a 60 min coronary occlusion when that was performed 30 min after the last short occlusion. This effect was lost after 1 h. Preconditioning could be renewed by a second cycle of brief coronary occlusion and reperfusion 4 d but not 1 h after the first cycle. These results suggest the release of a mediator from an exhaustible pool. Cardiovascular Research 1993;27:551-555