In the elderly cardiac size and function are determined by their level of physical activity. In this study, we assessed by echocardiography, the anatomic and physiologic changes of the heart in 28 elderly patients who had no cardiac disease and who were chronically bedridden. The data obtained were compared to those obtained from a control group of 38 age and sex matched elderly people whose activities had not been restricted. Chronically bedridden patients had markedly smaller left ventricular dimensions in both end-diastole and end-systole and smaller left atrial dimensions than did control subjects (3.7±0.7 vs 4.7±0.6cm, p<0.001, 2.4±0.8 vs 2.9±0.7cm, p<0.02 and 3.2±0.5 vs 3.8±0.9cm, p<0.01, respectively). Though the wall thickness of the interventricular septum did not differ between the study groups, the left ventricular posterior walls of the bedridden group were significantly thinner than in the control group (0.8±0.2 vs 1.0±0.2 cm, p<0.01). The bedridden group had a significantly lower stroke index (26.9±6.2 vs 47.0±11.1 ml/m², p<0.001) and cardiac index (1.84±0.52 vs 3.15±0.63 l/min/m², p<0.001) than did the control group. Left ventricular mass index and left ventricular systolic stress were significantly lower in bedridden patients than in control subjects (88.0±18.1 vs 143.5±30.9 g/m², p<0.001, and 135.9±4.9 vs 186.6±35.7 103 dynes/cm², p<0.001, respectively). The shortening fraction, however, did not differ between the two groups. The peak trans-aortic flow velocity of bedridden patients was not different from control subjects. The peak trans-mitral flow velocity in early diastole (R) of bedridden patients was significantly lower than in control subjects(0.44±0.15 vs 0.57±0.20 cm/s, p<0.01), while the decrease in peak trans-mitral flow velocity during atrial systole (A) was not significant. The ratio of A to R was significantly larger in the bedridden group than in the control group (1.8±0.7 vs 1.5±0.5, p<0.05). We conclude that long term bed rest causes disuse atrophy of the heart in the elderly by decreasing venous return, left ventricular work and wall stress.

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The purpose of this study was to determine whether computed tomography (CT) can detect hemorrhagic infarction occuring after intracoronary thrombolytic theraphy (ICT) for acute myocardial infarction (AMI). In an experimental study, 12 dogs underwent 2-4 h of left anterior descending artery (LAD) occlusion, followed by reperfusion, and infusion of contrast material into the LAD. After CT examination, the heart was cut into transverse sections. A good correlation was obtained between the CT-enhanced area and the hemorrhagic area in the sliced heart section (r=0.895, p<0.001). In a clinical study, we applied CT immediately after ICT in 25 patients with AMI. In 13 of 25 patients, the CT showed post-ICT myocardial enhancement areas. To evaluate the relationship of the enhancement areas shown by CT to the viability of the myocardium, we compared enhancement areas by CT with the corresponding perfusion defect areas of Thallium-201 imaging (SPECT) one month later. There was no significant corrlation between the enhancement areas and perfusion defect areas (r=0.38, p>0.1). The SPECT defect areas were consistently smaller than the CT enhancement areas. These results indicate that CT can detect hemorrhage into the myocardium after ICT, and that after ICT half the AMI patients showed hemorrhagic infarction. However, hemorrhage did not cause complete deterioration of the myocardium.

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We assessed the effect of stopping smoking on future cardiac events (cardiac death and non-fatal myocardial infarction (MI)) in 90 male smokers with previous MI by a prospective follow-up study. At the time of enrollment, the patients were divided into 2 groups according to their current smoking status (Group A: those who had stopped smoking (n=60), and Group B: those who were still smoking (n=30)). Follow-up was performed prospectively by annual postal questionnaires. During the mean follow-up period of 3.1 ± 1.4 years, 13 cardiac events (11 cardiac deaths and 2 cases of non-fatal MI) occurred in the 87 evaluable patients. The cardiac event rates in Groups A and B were 8.5% and 28.6%, respectively, and the relative risk was 3.4 (Group A vs B, p<0.05) by univariate analysis. The relative risk using multivariate analysis (Cox) was also statistically significant (3.1, p<0.05). HDL-cholesterol was significantly lower in Group B than in Group A, but other coronary risk factors apart from smoking were not significantly different between the two groups. At the end of the follow-up period, 89.8% of the patients in Group A remained nonsmokers and 21% of the patients in Group B had stopped smoking. Conclusion: Stopping smoking significantly reduced the risk of future cardiac events in male smokers with previous MI. This prospective follow-up study demonstrated that a significant reduction in the risk of future cardiac events could be achieved by stopping smoking in this group of patients.

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The purpose of this study was to investigate the relationship of dipyridamole-induced ST changes to the severity of coronary artery disease. The subjects were 100 patients without myocardial infarction who underwent coronary arteriography for the diagnosis of coronary artery disease. The dipyridarnole injection test (D) (0.568 mg/kg/4 min), and symptom-limited treadmill exercise test (T) were performed separately. Body surface electrocardiographic mapping of 87 leads was performed in both tests. The incidences of significant ST depression &le; 0.10 mV, number of leads showing significant ST depression (nST) and the maximal voltage of ST depression (maxST) in D and T were compared to the number of diseased coronary arteries. In patients without significant coronary stenosis (0VD group), the incidence of ST depression in the dipyridamole test was significantly lower than that in the treadmill test (D 9% vs T 47%, p<0.01). While, in one vessel disease (1VD), two vessel disease (2VD), and three vessel disease (3VD)groups, there was no significant difference in the incidence of ST depression between the dipyridamole test and the treadmill test (in 1VD, D 44% vs. T 65%; in 2VD, D 67% vs. T 93%; and in 3VD D 93% vs. T, 96%). In the dipyridamole test, nST was 0.6±2.4 in 0VD, 4.5±6.9 in 1VD, 4.1±4.5 in 2VD, and 10.6±8.1 in 3VD. Significant differences were found between 0VD and 1VD (P<0.05), 0VD and 3VD (P<0.01). 1VD and 3VD (P<0.01), and 2VD and 3VD (p<0.01). The maxST in the dipyridamole test was 0.02±0.04 mV in 0VD, 0.10±0.12 mV in 1VD. 0.13±0.11 mV in 2VD, and 0.22±0.11 mV in 3VD. Significant differences were found between 0VD and 1VD (p<0.01), 0VD and 2VD (p<0.01), 0VD and 3VD (p<0.01), 1VD and 3VD (p<0.01), and 2VD and 3VD (P<0.01). For the diagnosis of 3VD, the dipyridamole ECG test had as high a sensitivity (93% vs 96%), higher specificity (68% vs 38%, p<0.01), and higher predictive accuracy (75% vs 54%, p<0.01) than the treadmill test. For the detection of one or more stenotic coronary arteries, the dipyridamole test had a lower sensitivity (70% vs 85%, p<0.05), but higher specificity (91% vs 53%, p< 0.01), and as high a predictive accuracy (77% vs 74%) compared with the treadmill test. This study demonstrated that the dipyridamole ECG test was useful in stratifying the severity of coronary artery disease. Dipyridamole ECG was both sensitive and specific for the detection of 3VD.

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The sum of ST-segment elevation (ΣST on V_2-4) was measured to evaluate ST-segment re-elevation during early convalescence in 57 patients with acute myocardial infarction. Following rapid ST-segment elevation resolution during the first 12 h, ΣST again increased in many patients without signs of reinfarction or pericarditis, reaching a maximum approximately 5 days after onset. The magnitude of this re-elevation (Δ ΣST) was less than 0.3 mV in 30 patients (group A), and 0.3 mV or more in another 27 (group B). Based upon left ventriculography, the global ejection fraction in group B decreased significantly from 51±10% at the acute phase to 46±10% at the chronic phase. No such decreases were seen for group A. Regional ejection fraction in the infarcted portion improved significantly from 28±13% at the acute phase to 35±14% at the chronic phase in group A, but did not improve in group B. In addition, the non-infarcted portion in group B showed a significantly reduced regional ejection fraction. These results suggest that myocardial expansion of the infarcted portion may contribute to ST-segment re-elevation, an ominous sign of left ventricular dysfunction soon after acute myocardial infarction.

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A 72-year-old female who underwent the extirpation of metastatic intraspinal tumor showed an extremely wide variation of blood pressure with recurrent episodes of syncope due to paroxysmal hypotension. Treatment of the patient with salt supplement and L-threo-3, 4-dihydroxyphenylserine, an exogenous precursor of norepinephrine, markedly improved the syncopal attack as well as the daily activity.

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The effects of calcium antagonists (verapamil and nicardipine) on central dopaminergic activity were investigated in vitro. Rat striatal slices prelabelled with (³H)dopamine and superfused with Krebs-solution were stimulated electrically at a frequency of 1 Hz. Exposure to verapamil (3.3 × 10^<-7gt:-1 × 10^-5M) significantly increased both basal and stimulation-evoked (³H)dopamine release in a concentration-dependent manner. Nicardipine produced no changes in stimulation-evoked (³H)dopamine release, although a high concentration of nicardipine slightly increased basal release of (³H)dopamine. Exogenously applied unlabelled dopamine (1 × 10^<-7gt: M) inhibited the stimulation-evoked (³H)dopamine release. Verapamil (1 × 10^-6M) significantly antagonized the capacity of the unlabelled dopamine to inhibit stimulation-induced (³H)dopamine release. The blockade of D₂-receptors by a preferential D₂-antagonist, sulpiride, reduced the facilitatory effect of verapamil on stimulation-induced (³H)dopamine release. Pretreatment with pertussis toxin, which interferes with the coupling of the inhibitory guanosine triphosphatebinding proteins to adenylate cyclase, significantly diminished the effects of verapamil on stimulation-induced (³H)dopamine release. The results of the present study show that verapamil (but not nicardipine) in-creased dopamine release in rat striatum, at least partially via interactions with the D₂-dopamine autoreceptors and the pertussis toxin-sensitive guanosine triphosphatebinding proteins. Furthermore, a close interaction between verap-amil and the dopamine receptors might partially explain the central effects of verapamil.

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This study investigated whether nifedipine administered in divided daily doses would diminish left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). We administered nifedipine (12 mg/kg/day) in 3 divided doses by gastric gavage to 15-week-old male SHR (n=10) for 4 weeks. Age- and sex-matched SHR served as controls (n=10). Left ventricular (LV) function was evaluated by LV catheterization and cardiac output was determined by the thermodilution method. Plasma renin activity (PRA) and plasma norepinephrine levels were measured. Nifedipine significantly decreased blood pressure (p<0.01), shortened time constant T (p<0.05), and increased cardiac output (p<0.05). Nifedipine did not impair the LV systolic and diastolic indices during acute afterload elevation with angiotensin II. LV weight was similar in the 2 groups of rats. While PRA was unaltered, plasma norepinephrine levels were higher in the nifedipine-treated rats (p<0.05). These data indicate that nifedipine in 3 divided doses reduced blood pressure in SHR without compromising cardiac function bud did not reverse LVH. The short hypotensive duration of nifedipine and its enhancement of sympathetic nervous activity may be responsible for the failure to reverse LVH, despite adequate blood pressure control.

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The effect of diltiazem on stunned myocardium was evaluated by measuring the myocardial uptake of ^99mTc-PYP (pyrophosphate) in open chest experiments with dogs. Myocardial stunning was induced by a 30 min ischemic occlusion of the anterior descending coronary artery. Regional wall motion was monitored by echocardiography of the epicardium for 2 h during reperfusion. After a 30 min occlusion of the coronary artery, it was reperfused and ^99mTc-PYP was injected, followed by ²⁰¹T1 2 h later. The ischemic area was defined by Evans blue dye, and the infarct area by TTC staining. No dogs showed infarcts or ²⁰¹T1 defects in this study group. Five dogs of the control-1 group (C1, ischemic area=19.1±3.2%) showed decreased regional wall motion during occlusion (15.5 ±3.5% of control), and a slow recovery from depressed motion after 2 h of reperfusion (20.3±9.3%) with uptake ratio (compared to the non-ischemic area uptake) of ^99mTc-PYP (4.96±2.28). In contrast, both groups with diltiazem infusion (20 μg/kg/min), started either 30 min before ischemia (D1 =5 dogs) or just after reperfusion (D2=5 dogs), showed significantly better recovery after 2h of reperfusion (D1:115.4±36.0%, D2:109.2±44.2%) than C1 (p<0.05), D1 and D2 groups also showed suppressed ^99mTc-PYP uptake ratio (D1:1.06±0.33, D2:2.34±2.05, p< 0.05 vs C1) in spite of comparable ischemic area. Four dogs with small ischemic area (C2:5.3±5.0%) did not show in-creased ^99mTc-PYP uptake (1.15±0.35), and regional wall motion after 2 h of reperfusion was 96.1±24.1% of the control value (p<0.05 vs C1). Thus. diltiazem was effective in enhancing the suppression of ^99mTc-PYP uptake in the stunned myocardium, and similar results were obtained for small ischemic areas. The protective effect of diltilazem appears to be strongly related to the mechanism of ⁹⁹mTc-PYP uptake.

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The effect of intermittent coronary sinus occlusion (ICSO) with a balloon-tipped catheter on coronary arterial flow and coronary sinus pressure (CUSP) dynamics were studied in open-chest dogs. During coronary sinus occlusion (CSO), CUSP gradually rose and finally reached a plateau, while left coronary arterial mean flow velocities decreased. After the release of CSO CUSP immediately returned to baseline values, and the flow velocities correspondingly increased over the baseline values (hyperemic response). The decrease in ratios of flow velocities during CSO were unrelated to the duration of CSO, whereas hyperemic responses were positively correlated with the CSO duration. In the repetitive application of CSO (ICSO), inadequately short duration of release period decreased the net volume of coronary arterial flow significantly. Moreover, hyperemic responses were abolished by maximal coronary vasodilation with intravenous adenosine, augmented by combination with coronary sinus retroperfusion and reduced by coronary arterial ischemia. These findings indicate the presence of a compensatory regulating mechanism in the coronary circulation during ICSO. We should attach much importance to this mechanism for the effectiveness of ICSO. To be accurate, the changes in coronary arterial flow as well as CUSP dynamics should be considered when choosing adequate occlusion-release intervals of ICSO.

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Moricizine (moracizine) is a new class I antiarrythmic drug which is undergoing a large scale clinical trial at present. A rat model was used to compare the effects of moricizine (5 mg/kg i.v), disopyramide (DSP 5 mg/kg i.v) and mexiletine (MXT 5 mg/kg i, v) on early ventricular arrhythmias occurring within 30 min after ligation of the left coronary artery. After intravenous administration, all three drugs slowed the heart rate significantly (p<0.01), and compared to the control group only moricizine significantly increased the systolic, diastolic and mean arterial blood pressures. The total number of premature ventricular complexes were as follows; control group (n=9); 1666±250 beats, moricizine group (n=7); 1645±417 beats (NS), DSP group (n=10); 325±155 beats (p<0.01 vs control) and MXT group (n= 10); 733±147 beats (p<0.01 vs control). The incidence of primary ventricular fibrillation, was significantly reduced by DSP and MXT (10% reduction and 20% reduction respectively) (p<(0.05), while morici-zine (incidence 80%) had no effect in comparison to the control group (incidence 90%). Death due to arrhythmia was completely abolished by DSP and MXT; although moricizine showed a slight tendency to increase the mortality rate, but the difference was not significant. In conclusion, moricizine has no obvious protective effect on early ventricular arrhythmias resulting from coronary artery occlusion in rats.

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This study was designed to investigate effects of quiescence by cessation of electrical stimulation during the first stage of reoxygenation on recovery of mechanical function from hypoxia-induced contractile dysfunction in papillary muscles and effects of the absence of cardiac output on myocardial energetic metabolism of post-ischemic hearts. (1) Regular contractions and postextrasystolic contraction were evoked. After 120 min hypoxia, muscles were reoxygenated. In muscles of quiescence during the first 30 min reoxygenation, the recovery of regular contractions was better than that in muscles in which programmed stimulation was continued. However, the quiescence had no effect on the recovery of postextrasystolic contractions from hypoxia-induced contractile dysfunction. (2) Isolated hearts were perfused either according to Langendorff technique or as working heart preparations. After 40 min ischemia, hearts were reperfused for 25 min. Although there was no difference in energy charge of myocardium between 2 modes of reperfusion, % incidence of sustained ventricular fibrillation in muscles in which non-working mode was maintained for the first step of re-perfusion was lower than that in which working mode was continued. We presume that the reduction of contractile work during the initial step of reperfusion is of value for cardio-protection.

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This study was designed to clarify the state of beta-adrenergic signal transduction and the disordered level of its transduction in hypertensive hearts, using myocardium from spontaneously hypertensive rats (SHR) as a generic model of essential hypertension. Beta-adrenergic receptor binding sites and dissociation constants in the extracted membranes of adult (70-100 days of age) SHR heart were not significantly different from those of Wistar-Kyoto (WKY) rats, the non-hypertensive control. The adenylate cyclase activities stimulated by isoproterenol with GYP, Nay and forskolin were significantly higher in SHR compared to those in WKY. To determine whether differences in signal transduction are natural or are a result of hypertension, we evaluated chronotropic responses in cultured cells of fetal hearts which had not been exposed to hypertension. Fetal cardiac muscle cells of SHR were more sensitive than WKY to isoproternol stimulation over a wide concentration range. However, there were no statistically significant differences between these two strains with respect to the density of binding sites. These results suggest that in the transduction of adrenergic signals, alterations distal to the beta-receptors are present in the adult hearts of hypertensive rats, and, that the adrenergic signal transduction is already exaggerated in the pre-hypertensive fetal stage.

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