References

10 (4), 201-212

Gangloff, J., Pouyet, J., Kern, D. and Dirheimer, G. (1984), A Quenched-Flow Apparatus Which Allows the Measurement of the Kinetics of A Reaction in One Stroke. Journal of Biochemical and Biophysical Methods, 9 (3), 201-213

Martin, R.B., Yeater, R.A. and White, M.K. (1981), A Simple Analytical Model for the Crawl Stroke. Journal of Biomechanics, 14 (8), 539-548

Senator, M. (1981), Why Sliding Seats and Short Stroke Intervals Are Used for Racing Shells. Journal of Biomechanical Engineering-Transactions of the Asme, 103 (3), 151-159

Kono, S., Ikeda, M., Tokudome, S., Nishizumi, M. and Kuratsune, M. (1985), Smoking and Mortalities from Cancer, Coronary Heart-Disease and Stroke in Male Japanese Physicians. Journal of Cancer Research and Clinical Oncology, 110 (2), 161-164

Bernstein, E.F. and Bardin, J.A. (1981), Preventing Stroke from Carotid-Artery Disease. Journal of Cardiovascular Medicine, 6 (11), 1085-&

Alderman, M.H., Madhavan, S., Stanback, M.E. and Davis, T.K. (1982), Relation of Blood-Pressure Response to Therapy and the Occurrence of Myocardial-Infarction and Stroke. Journal of Cardiovascular Pharmacology, 4 S251-S256

Samuels, M.A. (1982), When Heart-Disease Causes Stroke. Journal of Cardiovascular Medicine, 7 (4), 419-&

Scott, S.M., Sethi, G.K. and Bridgman, A.H. (1982), Perioperative Stroke During Carotid Endarterectomy - the Value of Intra-Operative Angiography. Journal of Cardiovascular Surgery, 23 (5), 353-358

Howe, P.R.C., Rogers, P.F., Morris, M.J., Chalmers, J.P. and Smith, R.M. (1986), Plasma-Catecholamines and Neuropeptide-y As Indexes of Sympathetic-Nerve Activity in Normotensive and Stroke-Prone Spontaneously Hypertensive Rats. Journal of Cardiovascular Pharmacology, 8 (6), 1113-1121

Fieschi, C., Argentino, C., Toni, D. and Pozzilli, C. (1988), Calcium-Antagonists in Ischemic Stroke. Journal of Cardiovascular Pharmacology, 12 S83-S85

Badwey, T.M., Rice, J.C. and Kerstein, M.D. (1988), Amputation As A Consequence of Stroke. Journal of Cardiovascular Surgery , 29 (5), 563-566

Grenadier, E., Azhari, H., Beyar, R., Dinnar, U., Markiewicz, W. and Sideman, S. (1989), Echocardiographic Determination of Left-Ventricular Stroke Volume Index - Comparison to 3-Dimensional Computer Reconstruction. Journal of Cardiovascular Technology, 8 (1), 5-14

Adams, R.J., Nichols, F.T., Mckie, V.C., Mckie, K.M., Stephens, S., Carl, E. and Thompson, W.O. (1989), Transcranial Doppler - Influence of Hematocrit in Children with Sickle-Cell Anemia Without Stroke. Journal of Cardiovascular Technology, 8 (2), 97-101

Waldemar, G., Vorstrup, S., Andersen, A.R., Pedersen, H. and Paulson, O.B. (1989), Angiotensin-Converting Enzyme-Inhibition and Regional Cerebral Blood-Flow in Acute Stroke. Journal of Cardiovascular Pharmacology, 14 (5), 722-729

Strauer, B.E. (1990), Beta-Blocking-Agents in Heart-Failure - Modern Concepts and Overview. Journal of Cardiovascular Pharmacology, 16 S129-S132.

Abstract: Heart failure is characterized by the inability of the myocardium to shorten sufficiently or to eject an adequate stroke volume to maintain normal perfusion of both the cardiac and the extracardiac organs. Irrespective of etiologic reasons, the depression of myocardial contractility represents one of the major mechanisms that contributes to low output in heart failure. Despite their intrinsic negative inotropic effects, beta-receptor-blocking agents have been used in numerous studies for treating the failing heart, especially in dilated cardiomyopathy and ischemic heart disease. In this regard, specific therapeutic aims of the use of beta-receptor- blocking agents in chronic heart failure have been described, e.g., reduction of an increased heart rate in tachycardia, blood pressure reduction in hypertensive heart failure, improvement of supraventricular and ventricular arrhythmias, depression of an increased sympathetic tone (e.g., in hyperthyrioidism, pheochromocytoma), increase in the amount of downregulated beta-receptors, and anti-ischemic effects in coronary artery disease. For chronic heart failure, therefore, some special indications may be established and may be individually used; for acute heart failure, only very rare indications are present (e.g., hypertensive crisis, life- threatening cardiac arrhythmias). The actual rationale for the use of beta-receptor blocking agents in heart failure is therefore analyzed with regard to pathophysiology, clinical effects, and clinical outcome of treated patients

Keywords: ABNORMALITIES/BETA-BLOCKADE/BLOCKADE/CARDIAC FAILURE/CARDIOMYOPATHY/EAST/PLASMA NOREPINEPHRINE/TREATMENT

Tanaka, S., Hayase, A., Hashimoto, A., Takagi, Y., Kondo, S., Hayashi, K., Yamamoto, M. and Iimura, O. (1990), Hypertension and Cardiovascular-Diseases in An Epidemiologic- Study in Hokkaido, Japan. Journal of Cardiovascular Pharmacology, 16 S83-S86.

Abstract: The present study describes the results from the 10-year follow-up data of a prospective epidemiological study for hypertension and cardiovascular diseases in two communities of rural agricultural districts in Hokkaido, Japan. The number of incidences of cerebrovascular accidents (CVAs) in persons who were normotensive, borderline hypertensive (BHT), untreated hypertensive (HT), well-controlled HT [blood pressure (BP) < 150/90 mm Hg], and poorly controlled HT (BP greater-than-or- equal-to 150/90 mm Hg) were 0.46, 3.24, 4.17, 3.49, and 12.76 per 1,000 person-years, respectively: CVAs were markedly high in poorly controlled HT persons. The winter-summer mean BP differences in the first year were significantly and positively correlated with the differences in mean BP between the tenth and the first year, and were significantly higher in the progression to hypertension group than in the nonprogression group in both towns. Multivariate analysis indicated that the winter-summer mean BP difference was a significant variable for indication of progression to hypertension. From these results, we concluded that (a) good control of hypertension could considerably prevent CVA, (b) cold environment may contribute to the prgression to hypertension, and (c) winter-summer variation in BP may preduct the future course of BP

Keywords: BLOOD-PRESSURE/CARDIAC ACCIDENTS/CEREBROVASCULAR ATTACK/EAST/FRAMINGHAM/HYPERTENSION/PREDICTOR OF HYPERTENSION/PROSPECTIVE EPIDEMIOLOGIC STUDY/STROKE MORTALITY/WINTER-SUMMER BLOOD PRESSURE VARIATION

Omae, T. (1990), Changing Pattern of Cardiovascular-Disease in the Japanese Population in Relation to Hypertension Control Programs. Journal of Cardiovascular Pharmacology, 16 S81-S82.

Abstract: The changing pattern of cardiovascular disease during the last 30 years in Japan is described. The most striking change was a reduction in deaths caused by hypertensive cerebral hemorrhage. There was no increase in ischemic heart disease in the rural area studied but such a trend was shown in the urban area. A change in risk factors for cardiovascular disease, reduction in blood pressure, and increase in serum cholesterol were more marked in the rural than the urban area. Institution of a hypertension control program and marked changes in lifestyle, including diet, could explain the relatively rapid change in the frequency and the type of cardiovascular disease, particularly cerebral stroke. The prevention of atherosclerotic complications such as cerebral infarction and ischemic heart disease is becoming a more important task in preventive cardiology

Keywords: COMMUNITY/HEART-DISEASE/HISAYAMA/HYPERCHOLESTEROLEMIA/ISCHEMIC HEART DISEASE/LONG-TERM PROGNOSIS/MILD HYPERTENSION/STROKE

Bolli, P., Buhler, F.R. and Mckenzie, J.K. (1990), Smoking, Antihypertensive Treatment Benefit, and Comprehensive Antihypertensive Treatment Approach - Some Thoughts on the Results of the International Prospective Primary Prevention Study in Hypertension. Journal of Cardiovascular Pharmacology, 16 S77-S80.

Abstract: Several major studies investigated the possibility of a primary preventive effect of beta-blockers. The International Prospective Primary Prevention Study in Hypertension (IPPPSH) compared a beta-blocker-containing vs. a non-beta-blocker- containing antihypertensive regimen in 6,357 moderate-severe hypertensive men and women treated over 3-5 years. Blood pressure (BP) control was comparable with either regimen. beta-Blocker treatment was associated with less hypokalemia, earlier electrocardiogram normalization, and fewer withdrawals for uncontrolled hypertension. In agreement with the Medical Research Council (MRC) trial on mild hypertension and the Heart Attack Primary Prevention in Hypertension (HAPPHY) trial, but at variance with the Primary Prevention Metoprolol in Patients with Hypertension (MAPHY) study, cardiac event rates were similar in beta-blocker-and non-beta-blocker-treated patients. With either regimen, in-study BP reduction was associated with a lower rate of stroke as well as of cardiac events. In a subgroup analysis, nonsmokers appeared to derive beta-blocker benefit, the results being similar to those of the MRC. Smokers required higher doses of drugs to achieve diastolic target pressure, had a higher heart rate and hematocrit, and a higher cardiac event rate than nonsmokers at any given level of diastolic pressure. Except for the MAPHY trial, these primary prevention studies do not support the concept of a cardiac primary preventive effect of antihypertensive beta-blockade but stress the importance of good BP control and a comprehensive risk factor prevention approach in the management of hypertensive patients

Keywords: ANTIHYPERTENSIVES/BETA-BLOCKERS/BLOOD-PRESSURE/CORONARY HEART-DISEASE/HAPPHY/HYPERTENSION/IPPPSH/MAPHY/MORBIDITY/MORTALITY/PRIMARY PREVENTION/SMOKING/THERAPY/TRIAL

Miall, W.E. (1990), Beta-Blockers Vs Thiazides in the Treatment of Hypertension - A Review of the Experience of the Large National Trials. Journal of Cardiovascular Pharmacology, 16 S58-S63.

Abstract: The effects of antihypertensive treatment on cerebrovascular disease and coronary artery disease (CAD) end points reported in the large-scale national trials have differed. All trials have shown stroke benefit, whereas CAD benefit has not been convincingly demonstrated in any. In three trials, the effects of thiazide- and beta-blocker-based regimens can be directly compared. In the MRC Treatment Trial for Mild Hypertension in Britain, the largest of the trials and the only one to compare these two classes of drugs with each other and with untreated controls, stroke benefit was significantly greater in the thiazide than in the beta-blocker group (p = 0.002). Indeed, the 70% reduction in fatal strokes and 65% reduction in nonfatal strokes suggested an effect on cerebral infarction as well as on cerebral hemorrhage. Opposing trends were found for CAD end points with beta-blockers and thiazides when compared with controls. For coronary events, sudden deaths, and ECG changes of infarction, significant differences were found between the reduced rates for those receiving propranolol and the higher rates for those receiving bendrofluazide. Weak evidence has been put forward by four trials-MRFIT, HDFP, the Oslo trial, and the MRC trial-suggesting that thiazide treatment for those who already have evidence of coronary disease may be harmful. In no case is the evidence conclusive, and it involves only a small (but important) subgroup. In the MRC trial, a nonselective beta-blocker, propranolol, provided greater CAD benefit as measured by the incidence of myocardial infarction, sudden death, and ECG changes, but only in nonsmokers. Hypotheses generated by these trials need further investigation

Keywords: BETA-BLOCKERS/DIURETICS/MILD HYPERTENSION/OSLO/RANDOMIZED/CONTROLLED HYPERTENSION TRIALS/THIAZIDES/TRIAL

Strandgaard, S. and Paulson, O.B. (1990), Pathophysiology of Stroke. Journal of Cardiovascular Pharmacology, 15 S38-S42

Keywords: EAST

Kannel, W.B. (1990), Influence of Multiple Risk-Factors on the Hazard of Hypertension. Journal of Cardiovascular Pharmacology, 16 S53-S57.

Abstract: Atherosclerosis and coronary artery disease (CAD) are now the commonest sequelae of hypertension and all clinical manifestations of CAD occur in excess in persons with elevated blood pressure. Risk increases in relation to the extent of blood pressure elevation whether this is in the systolic or diastolic component, at any age and in either sex. Even isolated systolic hypertension increases cardiovascular risk. Elevated pressures are often accompanied by lipid abnormalities, hyperglycemia, elevated fibrinogen, obesity, and ECG abnormalities, all of which augment the risk. These risk factors associated with hypertension influence the coronary risk potential more than the nature of the blood pressure elevation. Although blood pressure makes an independent contribution to CAD, the risk at any level of pressure is markedly influenced by the cardiovascular risk profile. In mild to moderate hypertension in particular, the risk of CHD is concentrated in those who have impaired glucose tolerance, increased total/HDL ratio, ECG abnormalities, and smoke cigarettes. One or more of these associated risk factors also predisposes to other cardiovascular sequelae of hypertension, including stroke, peripheral vascular disease, and cardiac failure. The presence of organ involvement indicated by proteinuria, evidence of impaired ventricular function, or left ventricular hypertrophy greatly escalates the risk and usually indicates a compromised coronary circulation. Most myocardial infarctions and sudden deaths occur prior to the appearance of such evidence. Hypertensive risk assessment requires consideration of the multivariate risk profile because of the interdependence of the risk factors. The nature and urgency of treatment is better determined from such a risk profile than from the blood pressure parameters alone. Optimal preventive management of hypertension requires more than normalization of the blood pressure if coronary sequelae are to be avoided

Keywords: CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR-DISEASE/FRAMINGHAM/HYPERTENSION

Sauter, A. and Rudin, M. (1990), Calcium-Antagonists for Reduction of Brain-Damage in Stroke. Journal of Cardiovascular Pharmacology, 15 S43-S47

Keywords: EAST

Delpozo, G., Davalos, P. and Yamori, Y. (1990), Cardiovascular Risk-Factors in 2 Ecuadorian Urban and Rural Populations. Journal of Cardiovascular Pharmacology, 16 S24-S25.

Abstract: We examined the specific hypotheses linking the intake of sodium, potassium, calcium, magnesium, and protein of blood pressure (BP) and the relationship between dietary factors and mortality from the major cardiovascular diseases (CVD) in the Ecuadorian populations. Two ecuadorian populations, the urban and the rural, were selected from Quito and Vilcabamba, respectively. From Quito: 87 men and 83 women; from Vilcabama: 71 men and 91 women aged 50-54 were randomly selected for BP measurement, 24-h urine collection, and blood sampling according to the Cardiovascular Disease and Alimentary Comparison (CARDIAC) Study protocol. Samples were analyzed at CARDIAC center in Izumo, Japan. Mean systolic blood pressure (SBP) was not much different in the two populations, but mean diastolic blood pressure (DBP) and body mass index (BMI) were significantly lower in Vilcabamba (p < 0.001). Mortality from stroke was higher in Vilcambamba, whereas coronary death rate was higher in Quito. Both sodium intake and sodium/potassium ratio were higher in Vilcabamba (p < 0.001). Protein intake and serum cholesterol were higher in Quito (p < 0.001). Urinary taurine excretion was higher in Quito. There was no difference in W3/W6 fatty acids ratio between the two populations. Multiple regression analyses of intracommunity correlation indicated that both SBP and DBP were highly significantly related with BMI in Quito and that urinary excretions were inversely related to SBP. Serum cholesterol was positively related to coronary death rate. Mortality from stroke was inversely related to both serum cholesterol and protein and was positively related to salt consumption

Keywords: BLOOD PRESSURE/CARDIAC/CARDIAC STUDY/ISCHEMIC HEART DISEASES/SERUM CHOLESTEROL/STROKE/URINARY SODIUM EXCRETION/URINARY TAURINE EXCRETION

Millar, J.A. and Lever, A.F. (1990), Blood-Pressure, Change in Blood-Pressure, and Cardiovascular Event Rates in Placebo-Treated Patients in the Medical-Research Council Trial. Journal of Cardiovascular Pharmacology, 16 S89-S91.

Abstract: The relationship between cardiovascular event rate (stroke + coronary events), entry blood pressure (BP), change in BP over 6 months, and other variables was examined in the 8,654 placebo-treated patients in the Medical Research Council (MRC) trial. Entry BP was greater than screening pressures and fell significantly after randomization to placebo. The entry pressure was significantly greater but the fall after entry was less in those who had a cardiovascular event during 5.5 years of follow-up. Thus, patients with high entry pressure that remained elevated during follow-up had the highest event rates. This pattern was marked for stroke but was also found for coronary events. Other variables strongly related to event occurrence were sex, age, and smoking habit. Discriminant analysis based on these variables correctly identified 67% of those who had an event but incorrectly classified 40% of the much larger group who did not. These results suggest that failure of BP to fall after screening examinations is a cardiovascular risk factor. Thus, high-risk patients may be identified by repeated measurements of BP before treatment is started

Keywords: CARDIOVASCULAR RISK FACTORS/HYPERTENSION/MRC TRIAL

Doyle, A.E. and Donnan, G.A. (1990), Stroke As A Clinical Problem in Hypertension. Journal of Cardiovascular Pharmacology, 15 S34-S37

Steiner, T.J. (1990), Naftidrofuryl After Acute Stroke - A Review and A Hypothesis. Journal of Cardiovascular Pharmacology, 16 S58-S61.

Abstract: With demographic change. Western populations are becoming older. The prolonged decline in incidence of stroke, already a very costly illness, may soon reverse. This paper briefly reviews medical treatments of acute stroke that have been popular in the past and finds that they have been generally of little value. The place of naftidrofuryl, a drug with a complex pharmacological profile that includes selective S2- receptor blockade, is discussed in greater detail. Two clinical studies have indicated that, although it may not alter death rate in acute stroke, naftidrofuryl therapy enhances recovery from the disabling effects of cerebral infarction. One important consequence of this is a potentially major reduction in time spent in hospital by stroke patients. Hospital bed occupancy has been identified as a principal component in the cost of stroke to health services. Drug treatments that reduce death rate without improving recovery in survivors have an opposite effect, as has been seen in an important trial of glycerol

Keywords: CEREBRAL INFARCTION/COST BENEFIT/DEXAMETHASONE/DISABILITY/EAST/GLYCEROL/HEMORRHAGE/HEPARIN/HOSPITAL BED OCCUPANCY/RANDOMIZED CONTROLLED TRIAL/RECOVERY/SEROTONIN/THERAPY/TREATMENT

Mundo, M.R. and Lozano, R. (1990), The Influence of Nicardipine in Patients with High-Risk of Stroke. Journal of Cardiovascular Pharmacology, 16 S16-S19.

Abstract: Blood pressure and clinical status of 1,736 patients with cerebrovascular disease were observed during 12 months of treatment with nicardipine. The most common diagnoses were chronic cerebral ischemia (53.2%), transient ischemic attacks (TIA; 25.1%), and cerebral infarct (8.7%); 50.1% of patients were classed as hypertensive [systolic blood pressure (SBP) greater-than-or-equal-to 160 mm Hg or diastolic blood pressure (DBP) greater-than-or-equal-to 90 mm Hg[. Most patients (91.2%) received a daily dose of 60 mg nicardipine. Additional treatments included diuretics (37%), beta-blockers (11.5%), other antihypertensive drugs (15.8%), platelet antiaggregants (25.1%), and cardiotonic drugs (15.1%). A total of 282 patients (16.2%) were lost to follow-up, 21 (1.2%) patients withdrew due to side effects, 32 (1.8%) died, and 9 (0.5%) patients had treatment interrupted due to concomitant illness. In the hypertensive subgroup, blood pressure (SBP/DBP) was reduced from a mean baseline value of 175 +/- 22/97 +/- 14 mm Hg to 152 +/- 17/85 +/- 11 mm Hg at 3 months and 149 +/- 23/81 +/- 11 mm Hg after 12 months of treatment. The incidence of TIA or stroke among these patients was reduced from 29 cases (3.5%) during the first 3 months to 11 cases (1.54%) during months 4-12 (p < 0.01). In normotensive patients there were 18 (2.15%) cases during months 1-3 and 13 (1.55%) cases during months 4-12 (difference not significant). In the 280 patients treated with nicardipine alone, the most frequent side effects during the first month were facial flushing (6.8%), gastrointestinal problems (5%), dizziness (3.2%), headache (3.2%), drowsiness (3.2%), and hypotension (1.1%). Most of these side effects were transient. These results demonstrate that nicardipine lowered blood pressure over the 12 months of observation. This may have contributed to the reduction in the incidence of TIA or stroke among hypertensive patients during months 4-12

Keywords: ANTAGONIST/HYPERTENSION/ISCHEMIA/RATS/TIA/VASODILATOR

Simpson, F.O. (1990), Fallacies in the Interpretation of the Large-Scale Trials of Treatment of Mild to Moderate Hypertension. Journal of Cardiovascular Pharmacology, 16 S92-S95.

Abstract: Data from large-scale trials of treatment of mild to moderate hypertension are being misinterpreted and unjustifiably extrapolated to general populations. The main errors include acceptance of "entry" pressures as typical in spite of evidence that true blood pressure was much lower, extrapolation of results in low-risk volunteers to the whole population, neglect of treatment given to the most endangered control subjects, and the assumption that the burden of side effects seen in a rigid high-dose trial is typical of that seen when the same or better drugs are used in clinical practice. The health risks of hypertension and the benefits conferred by antihypertensive therapy are being played down unjustifiably on the basis of inappropriate data

Keywords: ANTIHYPERTENSIVE TREATMENT/BLOOD-PRESSURE/CARDIOVASCULAR- DISEASE/COST BENEFIT/DECLINE/DRUG-TREATMENT/EAST/EXPLAIN/HYPERTENSION/NEW-ZEALAND/PREVENTION/STROKE MORTALITY/THERAPEUTIC TRIALS

Capon, A., Lehert, P. and Opsomer, L. (1990), Natfidrofuryl in the Treatment of Subacute Stroke. Journal of Cardiovascular Pharmacology, 16 S62-S66.

Abstract: In a placebo-controlled, double-blind study, 82 patients in the subacute stage of a disabling stroke were studied to assess the effect on clinical improvement of 600 mg naftidrofuryl against placebo. Forty-two patients were treated with the drug and 40 with placebo, in each case administered for 60 days. All patients received 100 mg aspirin and 300 mg dipyridamole daily and entered a similar program of rehabilitation therapy. At the start and the end of the study, the motor functions of the upper and lower limbs, the ability to walk and to perform daily activities, the comprehension and expression of speech, and the mental progress were assessed with quantitative linear scales. In the group treated with active drug, a greater overall tendency of improvement was observed, reaching statistically significant levels for walking and activities of daily life when compared to placebo-treated patients. Overall improvement was negatively influenced by advancing age, but the statistically significant effect of treatment on walking and daily activities was not interfered with by age. Right-sided lesions showed better improvement under active drug than left- sided lesions. This may be due to a correctional effect of naftidrofuryl on hemispatial neglect

Keywords: APOMORPHINE/HEMIPLEGIA/NAFTIDROFURYL/NAFTIDROFURYL TREATMENT/NEGLECT/RATS/REHABILITATION/SUBACUTE STROKE

Tuomilehto, J., Wikstrand, J., Warnold, I., Olsson, G., Elmfeldt, D. and Berglund, G. (1990), Coronary-Artery Disease Can be Prevented by Antihypertensive Therapy - Experiences from the Maphy Study. Journal of Cardiovascular Pharmacology,