Vasoconstrictors bind to their receptors on the cell surface to activate phospholipase C and Ca²⁺ channels, resulting in the mobilization of Ca²⁺ from intracellular are extracellular Ca²⁺ pools and protein kinase C activation. Vasoconstrictors are also thought to activate a distinct cellular mechanism for downregulating 20kDa myosin light chain (MLC₂₀) phosphatase activity, which involves Rho p21 and protein kinase C, resulting in an increase in the Ca²⁺ sensitivity of MLC₂₀ phosphorylation. Protein kinase C also appears to activate a MLC₂₀ phosphorylation-independent mechanism for contraction, contributing to the maintenance of agonist-induced contraction. On the other hand, vasorelaxants inhibit activation of phospholipase C and gating of Ca²⁺ channels, or stimulate Ca²⁺ extrusion across the plasma membrane, leading to a decrease in the [Ca²⁺]i. Vasorelaxants also appear to stimulate MLC₂₀ phosphatase activity, resulting in a further reduction of contractile response. The modulatory mechanism for changing the Ca²⁺ sensitivity, together with the major regulatory mechanism for cellular Ca²⁺metabolism, plays an important role in regulating vascular smooth muscle tone.

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Although the pathogenesis of essential hypertension still remains unclear, it is now generally accepted that the kidney is deeply involved in the pathophysiology of this disease.
This paper therefore, reviews current knowledge of the role of renal dopaminergic activity in essential hypertension. This is believed to be one of the most important renal diuretic and depressor systems.
Suppression of urinary excretion of free dopamine (DA) is observed in essential hypertensives, particularly in those with low plasma renin activity (LRH) who demonstrate body fluid volume expansion. An increased natriuretic response to exogeneously administered DA is found, particularly in LRH, and suppressed biosynthesis of DA from L-dopa in the kidney has been suggested. Furthermore, this suppression of renal dopaminergic activity was also observed in young normotensive subjects with an apparent family history of hypertension before any evidence of hypertension emerged.
From these findings, it is concluded that the decrease in renal dopaminergic activity is involved, at least in part, not only in the pathophysiology of essential hypertension, but also in the pathogenesis of this disease.

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Convincing evidence is now available suggesting that several unfavorable cardiovascular events respect a well-defined diurnal pattern in their occurrence. In particular, ischemic heart disease has been widely investigated, and many data indicate a constellation of underlying risk factors whose temporal coincidence might act as triggering factors in the occurrence of acute events. In this paper, the recent knowledge concerning both epidemiology of ischemic heart disease and potentially favoring factors are reviewed from a chronobiological point of view.

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The blood flow velocity of the right brachial artery was measured noninvasively by pulsed Doppler flowmetry in 50 patients with angina pectoris. Reactive hyperemia was induced by a 2-minute occlusion of the artery by a tourniquet. We assessed the peak velocity ratio (PVR) and 50% recovery time (RT) which were defined as the ratio of maximal to baseline systolic peak velocity and as the interval from the resumption of arterial flow to 50% decline of the increased systolic peak velocity, respectively. Multiple regression analysis for determinants of PVR and 50% RT was performed with 7 variables which were age, sex, hypertension, diabetes mellitus, smoking, total cholesterol level, and the number of diseased coronary arteries. Multiple R was 0.649 (p<.01) for PVR and 0.682 (p<.01) for 50% RT. There were significant inverse cor-relations between PVR and the number of diseased vessels (t-value; -3.34), hypertension (-2.43) and smoking (-2.38). The 50% RT was inversely corre-lated with the number of diseased vessels (t-value; -4.45), feminine gender (-2.75) or smoking (-2.12). Stepwise regression analysis revealed that the number of diseased vessels was the only significant variable for the determination of PVR or 50% RT. An impairment of reactive hyperemia at the forearm vessel correlated with the severity of coronary artery disease in patients with angina pectoris. This finding suggests the presence of some identical mechanisms which are detrimental to both vascular beds. Observation of the hyperemic response at the brachial artery will provide a clue for noninvasive estimation of the extent of coronary artery disease.

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Background: Preliminary study to test the feasibility of pharmacological stress testing during cardiac catheterization, thus combining anatomical and functional information.
Patients and methods: 21 consecutive patients with known or suspected coronary artery disease, referred for diagnostic catheterization. Biplane ventriculography was performed before and during dobutamine infusion. The patients were subdivided into 3 groups: Group I (n=11, 52%) with at least one territory supplied by a significantly stenosed coronary artery and showing normal resting regional wall motion. Group II (n=6, 29%) patients in whom the affected vessel(s) supplied exclusively a territory with regional wall motion ab-normalities at rest. Group III (n=4, 19%) had no significant coronary artery disease and served as control.
Results: In group I, 9/11 (82%) patients and in group II, 3/6 (50%) patients showed either ischemia or viability reactions or both after dobutamine stress. Overall, substantial functional information was gathered in 12/17 patients (71%). Control patients showed no worsening of regional wall motion under dobutamine. Neither global left ventricular ejection fraction nor left ventricular end diastolic pressure were as accurate in detecting ischemia as regional wall motion analysis. In patients who had only ischemia and no viability reaction as judged by regional wall motion analysis, ejection fraction fell significantly in 4/6 (67%) patients; end diastolic pressure on the other hand rose significantly in 3/6 (50%).
Conclusions: Dobutamine stress testing performed during cardiac catheterization is convenient, feasible and safe and yields clinically useful infor-mation in a high percentage (71%) of patients with significant coronary artery disease. Further experience is needed to evaluate the sensitivity, specificity and predictive value of this new approach.

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Objective. The purpose of this study was to determine whether warming of exercising legs improves exercise capacity in patients with cardiac disease and low exercise tolerance. Background. Exercising muscle temperature reflects both muscle metabolic rate and muscle blood flow. Increase in muscle temperature in exercising legs is impaired in patients with chronic heart failure. We hypothesized that the mechanisms responsible for impairment of temperature increase in exercising muscle might be related to those responsible for low exercise tolerance. Methods. We studied 17 patients with cardiac disease whose anaerobic threshold (AT) ranged from 6.6 to 14.8ml/kg/min (mean 11.2±1.9 SD). Subjects performed symptom-limited sitting cycle ergometer exercise with or without warming of the thighs. Both thighs were warmed by use of hot packs fixed by supporters. To determine the effect of the supporters themselves on AT and peak VO₂, the same ergometer exercise was performed by 7 patients with or without supporters. Peak VO2 and AT were determined by concomitant respiratory gas monitoring. Results. 1) Warming of the thighs increased deep temperature in the thighs (1.0∼2.8°C). 2) AT and peak VO₂ were significantly improved in the warming exercise compared with the non-warming exercise (p<0.01, p<0.01). 3) There was no significant difference in AT or peak VO₂ between the exercises with and without supporters. Conclusion. The findings of this study indicate that warming of exercising legs improves exercise capacity in patients with cardiac disease and low exercise tolerance.

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To determine the possible mechanism of the ischemic-like electrocardiogram (ECG) during exercise in the presence of anginal chest pain and normal coronary angiograms, both a treadmill exercise test (TET) and coronary hemodynamic study were prospectively performed in 33 consecutive patients (18 females and 15 males, aged 48±10 years) with angina of unknown cause. Although baseline characteristics and coronary hemodynamics were similar between patients with (TET+, n=17) and those without (TET-, n=16) ischemic-like ECG during TET, effort angina was more frequently seen in the former group (p<0.01). Compared to TET-patients, TET+patients had a significantly lower maximum great cardiac vein flow (GCVF, 108.8±47.0 vs 146.4±23.4ml/min, p=0.007), higher minimum coronary vascular resistance (0.94±0.41 vs 0.61±0.09mmHg/ml/min., p=0.003), and lower corrected GCVF (GCVF/rate-pressure product, 0.0087±0.0036 vs 0.0125±0.0019, p=0.001) after dipyridamole infusion (0.56mg/kg for 4min.). Though coronary flow reserve was significantly lower in TET+than in TET-patients (2.26±0.59 vs 3.08±0.48, p=0.0001), myocardial oxygen consumption and myocardial efficiency (rate-pressure product/myocardial oxygen consumption) were still similar between these two groups after dipyridamole infusion. Thus, coronary microvascular dysfunction rather than altered cardiac metabolism could contribute to effort angina and ischemic-like ECG during exercise in patients with anginal chest pain and normal coronary angiograms.

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The normal shape of the T wave on the standard 12-lead electrocardiogram (ECG) is asymmetrical. The spatial velocity electrocardiogram (SVECG) is a method of recording the slope of the wave of the ECG and makes it possible to quantify the symmetry of the ECG-T wave. The aim of this study was to diagnose resting effort angina pectoris not detectable by conventional resting ECG using SVECG. We studied SVECG-T waves in effort angina pectoris patients with significant coronary artery stenosis but with normal resting ECG (AP group: 50 subjects) and in an age- and sex-matched normal controls (N group: 30 subjects). The SVECG is depicted as a simple differential wave, and all SVECG-T waves had two peaks. The first peak of the SVECG-T wave was designated as the 'a' wave and the second peak as the 'c' wave. The heights (a wave-mag, c wave-mag) and c wave-mag/a wave-mag ratio (c/a ratio) were calculated. The c/a ratio was significantly decreased in the AP group (1.52±0.29 vs 1.87±0.27, p<0.0001). In cases below the cut off c/a ratio of 1.7, the diagnostic sensitivity, specificity and accuracy for effort angina pectoris were retrospectively evaluated to be 82%, 70% and 78%, respectively. The heights of the 'a' and 'c' waves correspond to the maximum slope of the ascending and descending limbs of the T wave on ECG. The symmetrization of the T wave on ECG is considered to occur when the c/a ratio decreases and approaches 1.0. In conclusion, the c/a ratio of the SVECG-T wave is a useful index to diagnose effort angina pectoris at rest when the resting ECG is normal.

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We retrospectively reviewed all patients with a final diagnosis of deep venous thrombosis (DVT) treated at Linkou Chang Gung Memorial Hospital between 1989 and 1995. There were a total of 245 patients with a mean age of 58 years (males 56 and females 59), ranging from 11 to 89 years. The ratio of left to right leg involvement was 2.4 to 1 (166 to 71), however, the right leg was more likely to lead to an acute pulmonary embolism, with a ratio of 3.0 to 1 (9/71 to 7/166 patients). Among these patients, 16.3% (40) had cancer. The most frequently involved system was the GI system (16). Adenocarcinoma proved the most common type of malignancy 62.5% (25/40).
From this analysis, we found the left leg had a higher likelihood of thrombosis but a DVT of the right leg was more frequently associated with an acute pulmonary embolism. As with previous reports there was a strong relationship between cancer and DVT and the development of a deep venous thrombosis requiring a search for an underlying malignancy in those patients with an unexplained DVT.

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594 blood donors were studied to define the influence of regular blood donation on blood pressure. Blood pressures were compared at the first phlebotomy performed at the Padova Blood Unit, the 13-year phlebotomy, and the median between the two. As a control population, a cohort of 594 non-donors from the same general population similar to the blood donors was studied twice at a 15-year interval.
Subjects had made on average 7.3±0.4 donations at the first step, 23±0.6 at the second, and 30.9±0.7 at the last step. Unadjusted systolic blood pressure regularly and significantly increased by 1.6% from the first phlebotomy to the second one and by 2.3% from the first to third. Adjusted systolic blood pressure, on the contrary, significantly decreased by 2.1% and by 2.7% respectively. Diastolic blood pressure tended to increase insignificantly, while the adjusted one did not change at all. The increase of systolic blood pressure from the first to second step directly correlated with the number of donations, and this also applied to differences between the first and the third. When the increase in age was introduced in the multiple regression analysis, systolic blood pressure rise from the first to third step showed an inverse correlation with the number of phlebotomies.
Our data render suspect the results of epidemiological investigations which took into consideration cohorts of blood donors; although these cohorts may be anagraphically representative of a general population, repeated phlebotomies introduce a bias leading to the detection of misleadingly low blood pressure values in regular blood donors.

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The therapeutic effects of interferon in chronic hepatitis C and many of its adverse effects have been well documented. However, there are only a few reports regarding its adverse effects on the cardiovascular system. The aim of this study was to clarify the clinical features of the adverse effects of interferon on the cardiovascular system in patients with chronic hepatitis C. We monitored 295 patients with chronic active hepatitis C during 312 courses of interferon therapy and for 1 year after the end of treatment for the presence of cardiovascular adverse effects. We found 6 patients with cardiovascular adverse effects during interferon therapy and 4 more patients within 1 year after the end of therapy (10/312, 3.2%). The adverse effects of interferon on the cardiovascular system included arrhythmia (n=4), ischemic heart disease (n=4) and myocardial disease (n=2). None of the clinical factors, including history of cardiovascular disease, were related to these cardiovascular adverse effects. In all instances the patient's condition improved after discontinuation of interferon and adequate therapy. The cardiovascular adverse effects of interferon occurred frequently in patients with chronic hepatitis C, even after the end of therapy and they were unpredictable. Thus, all patients undergoing interferon therapy should be monitored not only during but also after the end of treatment.

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There is abundant evidence that the atherosclerotic process begins in childhood. Dyslipidemia is a major risk factor for atherosclerosis in adults and children. In the present study, we measured serum lipoprotein concentrations in 194 healthy children aged between 4 to 14 years. Children were grouped according to the socioeconomic status of the families, family history of essential hypertension and passive tobacco exposure. The values of total cholesterol, low density lipoprotein cholesterol and the ratio of total cholesterol/high density lipoprotein cholesterol in the low socioeconomic group were found to be significantly higher than the values obtained for the middle-high socioeconomic group. The values of total cholesterol, low density lipoprotein cholesterol, the ratio of total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol in the passive smoker group were found to be significantly higher than those of the non-smoker group. But, the socioeconomic level in the passive smoker group was found to be significantly lower than that of the nonsmoker group, and therefore, the impact of passive smoking on the serum lipids in children was related to socioeconomic status. A significant difference in terms of blood lipid fractions between the groups with and that without a family history of essential hypertension was not found.
These results suggest that passive smoking and lower socioeconomic status are important risk factors for cardiovascular heart disease, while a positive family history of essential hypertension is not an important risk factor.

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An 18-year-old schizophrenic female was recently treated after overdosing on trihexyphenidyl, thioridazine and an unknown antidepressant. On presentation to a local hospital, she was cyanotic with dilatated pupils and in acute respiratory failure. She was intubated prior to transfer. While in our Emergency Department, she exhibited occasional premature ventricular contractions which later became intermittent torsade de pointes. As this was an anticholinergic overdose we infused sodium bicarbonate in an attempt to increase protein binding, hoping to decrease the concentration of toxic metabolites. We also tried to suppress the dysrhythmia by infusing magnesium. The potassium level was borderline low so a supplemental infusion was initiated. Defibrillation was attempted. To try to shorten the action potential duration by activating the K⁺ channel, an isuprel infusion was also attempted. All methods failed. The patient fluctuated between an irregular sinus rhythm with prolonged QT interval and pulseless torsade de pointes for almost 24 hours. At all times, she responded appropriately to pain. Finally we attempted blockade of the calcium channel using verapamil with dramatic results. Each single bolus (0.1mg/kg) successfully converted the patient back to sinus rhythm for some 15-20 minutes before the torsade recurred. After the initiation of a continuous verapamil infusion (0.005mg/kg/hr), the patient remained in stable sinus rhythm.
Verapamil proved highly effective in this patient with an anticholinergic overdose induced dysrhythmia.

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