Forearm arterial distensibility in systolic hypertension.

It is unclear whether the stiffened arterial tree in systolic hypertension is the cause or the effect of the disease. In this study, brachial and radial arterial pulses were sensed by external Pixie transducers and measurements of pulse wave velocity converted to volume distensibility using the Bramwell-Hill equation. Blood pressure was controlled as a variable by repeating the measurements at a variety of transmural arterial pressures. This was accomplished by encasing the forearm in a rigid plastic cylinder within which pressures were varied. Twenty-nine patients with systolic hypertension were compared with 22 age-matched control subjects. At ambient pressures the volume distensibility of patients was lower than that of control subjects (0.10 versus 0.18% delta volume/mm Hg, p less than 0.001) but there was no difference in volume distensibility between the two groups at any comparable transmural pressure. Nineteen patients were treated for 1 month with a thiazide diuretic agent and the studies were then repeated. Systolic and diastolic blood pressure decreased significantly and volume distensibility increased (0.10 to 0.15% delta volume/mm Hg, p less than 0.001) at ambient pressures. But at comparable transmural pressures, volume distensibility was unchanged. It is concluded that, in the forearm, increased arterial stiffness is the result and not the cause of systolic hypertension, but these data cannot exclude increased aortic stiffness as a significant factor. Thiazide diuretic drugs increase forearm arterial compliance by lowering blood pressure without a demonstrable drug effect on this arterial wall.

Systolic hypertension. Direct and indirect BP measurements.

The BPs of each of 26 patients with systolic hypertension were simultaneously measured indirectly by the cuff-mercury sphygmomanometer (cuff) and directly by intra-arterial recording from a brachial artery. The systolic BPs recorded by the two methods were comparable, indicating that systolic hypertension can be reliably diagnosed by readings from the cuff alone. However, the average diastolic BP was significantly overestimated by the cuff. This error in turn led to an underestimation by the cuff of the pulse pressure and overestimation of the mean arterial pressure. Thus, the low intra-arterial (true) diastolic BP and wide pulse pressure make increased arterial stiffness a plausible contributing factor in the pathophysiology of systolic hypertension.

Effects of tiodazosin, a new antihypertensive, hemodynamics and clinical variables.

Tiodazosin, a new antihypertensive, resembles prazosin in structure and alpha-adrenergic-blocking activity, and it also exerts a direct vasodilator effect. We evaluated its long-term hemodynamic and systemic effects in patients with essential hypertension. Our data show that after 10 wk of therapy with tiodazosin, 7 of our 10 patients had significant reduction in intra-arterial mean blood pressure as a result of a fall in systemic vascular resistance. Heart rate, cardiac output, and plasma volume did not change. Systemic effects were minor and included a gain in weight and a reduction in hemoglobin, hematocrit, platelet count, serum protein, albumin, bilirubin, and specific gravity of urine. No patient initially developed orthostatic symptoms after the first dose, but there were transient episodes of light-headedness in three patients, palpitations in two, increased urinary frequency in one, and drooping of eyelid in another during the trial period. One patient developed profound orthostatic hypotension, which could be attributed to the drug. Because of such side effects and the failure to lower blood pressure in 30% of patients with essential hypertension, tiodazosin appears to have several important drawbacks and little advantage over currently available antihypertensives.

Nifedipine in chronic cor pulmonale: acute and relatively long-term effects.

After 20 mg sublingual nifedipine in 12 men with clinical stable chronic cor pulmonale the mean arterial pressure and systemic vascular resistance fell, cardiac index rose, and mean pulmonary arterial (Ppa) and wedge (Ppaw) pressures, right atrial pressure, and PaO2 remained unchanged. After 20 mg orally every 6 hours for 24 hours in 11 patients, the mean arterial pressure fell further, systemic vascular resistance remained low, and the cardiac index returned to baseline, whereas the Ppa and Ppaw decreased, but the pulmonary vascular driving pressure (Ppa-Ppaw), right atrial pressure, PaO2, and spirometry and ejection fractions remained unchanged. Of eight patients receiving maintenance therapy four developed untoward side effects in 1 to 3 weeks and one was noncompliant. The remaining three patients evaluated at 6 weeks failed to improve and had unchanged resting hemodynamics. Thus in the absence of a potentially reversible hypoxic pulmonary hypertension, nifedipine may not improve pulmonary arterial pressure and cardiac function in clinically stable patients with cor pulmonale.

Lack of relationship between plasma insulin and glucagon levels and angiographically-documented coronary atherosclerosis.

In 120 consecutive patients undergoing diagnostic coronary arteriography, fasting blood glucose, plasma insulin, glucagon, serum cholesterol and triglyceride concentrations were measured. The insulin-glucose ratio and insulin-glucagon ratio were calculated. Forty-five patients had normal coronary arteries, 19 had single vessel coronary artery disease and 56 patients had multiple vessel disease. Fasting blood glucose was greater than 120 mg/100 ml in 37 patients (group A) and included 9 of the 10 known diabetics, 3 of whom were being treated with insulin. Seventy-seven patients included in group B had fasting blood glucose concentration less than 120 mg/100 ml. Patients with multiple vessel coronary disease in either group had higher blood glucose and cholesterol concentrations than those with normal coronary arteries or the ones with single vessel disease, but they did not have higher plasma insulin or glucagon levels nor increased insulin-glucose or insulin-glucagon ratios. With comparable extent of coronary artery disease patients in group A had higher plasma insulin levels and insulin-glucagon ratios than those in group B, but no correlation exists between the presence or extent of coronary atherosclerosis and these variables in either group. Thus, neither fasting plasma insulin level nor insulin-glucagon ratio predicts the status of underlying coronary atherosclerosis in either diabetics or nondiabetics.

Atrial natriuretic peptide response to cardioversion of atrial flutter and fibrillation and role of associated heart failure.

Plasma atrial natriuretic peptide (ANP) concentrations were measured before and 1 hour after cardioversion in 40 patients (27 with atrial flutter and 13 with atrial fibrillation) admitted for elective cardioversion. Fourteen (11 with atrial flutter and 3 with atrial fibrillation) had clinical evidence of congestive heart failure (CHF). Conversion to sinus rhythm was successful in 39 patients. The mean ANP concentration in the entire group decreased after cardioversion from 38 +/- 4 to 17 +/- 2 pmol/liter (p less than 0.001). In the subgroup with CHF, the ANP level, which was not significantly higher than that in the group without CHF, decreased from 47 +/- 8 to 19 +/- 3 pmol/liter (p less than 0.01). Neither mode of cardioversion (spontaneous 1, pharmacologic 2 and direct-current countershock 36) nor associated CHF influenced ANP response to cardioversion. One patient with atrial flutter and "failed cardioversion" had unchanged ANP level. The decrease after cardioversion in ANP concentration correlated with its control level (r = 0.88, p less than 0.001) but not with the decrease in heart rate. The ANP level in patients with atrial fibrillation was 45 +/- 9 vs 38 +/- 5 pmol/liter in those with atrial flutter (difference not significant). Arrhythmia duration, left atrial size, and ventricular rate or arterial blood pressure did not correlate with ANP concentration in any subgroup. It is concluded that (1) the ANP level is elevated comparably in patients with both atrial flutter and fibrillation regardless of the presence or absence of CHF; and (2) the level decreases, independent of the mode of cardioversion or presence of CHF, promptly after successful cardioversion.

Systemic systolic hypertension in the elderly: correlation of hemodynamics, plasma volume, renin, aldosterone, urinary metanephrines and response to thiazide therapy.

Twenty-four men, mean age 63 +/- 1.7 years, with systemic systolic hypertension were studied before and after 1 month of therapy with oral hydrochlorothiazide, 50 mg/day. The control mean plasma volume was 2,664 +/- 96 ml, cardiac index 3.9 +/- 0.2 liters/min/m2, stroke volume index 52 +/- 2 ml/beat/m2, systemic vascular resistance 1,351 +/- 80 dynes s cm-5, plasma aldosterone 8.6 +/- 1.0 ng/dl and 24-hour urinary excretion of metanephrines 0.371 +/- 0.044 mg. On renin-sodium profiling in 23 patients, 12 were classified into a normal group and 11 into a low-renin group; none had high renin values. Based on multiple regression analysis, the 24-hour urinary excretion of total metanephrines appeared to be the single most important factor explaining 28% of the variability in systolic blood pressure (BP). After therapy with oral hydrochlorothiazide, the elevated systolic BP decreased (p less than 0.0001) and diastolic BP decreased (p less than 0.005), with concomitant reduction in systemic vascular resistance (p less than 0.03). Patients in both the normal- and low-renin groups had normal plasma volume and responded similarly to thiazide diuretic therapy, without symptomatic side effects.

Baroreflex function during 45-degree passive head-up tilt before and after long-term thiazide therapy in the elderly with systolic systemic hypertension.

The ratio of the 30th to the 15th cardiac cycle duration on an electrocardiogram (30:15 ratio) immediately after active standing from the supine position has been used as one of the markers of baroreflex function. A ratio of < or = 1.0 has been suggested to indicate baroreflex dysfunction. Blood pressure (BP) changes were measured and the 30:15 ratio was calculated after standing and during 45-degree passive head-up tilt from the supine position in 10 nondiabetic men (mean age +/- SE 70.1 +/- 1.05 years, and BP < 150/90 mm Hg). After tilt the decrease in systolic BP (from 132 +/- 4.8 to 117 +/- 6.3 mm Hg; p < 0.001) appeared to be larger than that after standing (from 132 +/- 4.6 to 123 +/- 5.8 mm Hg; p < 0.01), whereas the 30:15 ratios were 0.965 +/- 0.006 and 0.970 +/- 0.014, respectively, which suggested baroreflex dysfunction. Although the mean of the 2 ratios did not differ, the variance appeared to be less during tilting than after standing. Thus, the 45-degree passive head-up tilt appeared to be a better and more uniform inducer of orthostatic stress than active standing. Therefore, 45-degree head-up tilt was used in a group of 10 nondiabetic male patients (aged 70 +/- 1.46 years) with isolated systolic hypertension (systolic BP > 160 mm Hg, diastolic BP of < 90 mm Hg) to assess their baroreflex function. Upon tilting, their systolic BP decreased from 190 +/- 5.5 to 179 +/- 5.8 mm Hg (p < 0.05) and their 30:15 ratio was 0.985 +/- 0.011.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic response to orthostatic stress in the elderly with systolic systemic hypertension before and after long-term thiazide therapy.

The hemodynamic effects of orthostatic stress in elderly subjects with systolic hypertension were studied before and after long-term hydrochlorothiazide therapy (50 mg daily). Sixteen nondiabetic men aged 70 +/- 1 (SE) years participated in the study initially, and 12 completed 1 year of therapy. Patients underwent 45 degrees head-up incline on a tilt table before, after 1 month and after 1 year of therapy. Hemodynamic variables were measured in the following situations: (1) the supine position, (2) immediately after completion of passive 45 degrees head-up position at 0 minute, (3) at 15 minutes in the tilted state while patients performed intermittent foot movements to minimize gravitational pooling and simulate the standing position outside the laboratory, and (4) after returning to the supine position. Systolic and diastolic blood pressure (BP) decreased significantly after 1 month of therapy, and this reduction was maintained up to 1 year in all aforementioned body positions, with the exception of diastolic BP at 0 minute of tilt, which was significant at 1 year only. Before therapy was begun, there was a significant reduction in systolic BP immediately after completion of tilting; however, this was statistically insignificant both at 1 month and 1 year of therapy. Thus, the data may help dispel the concern of exacerbating the hypotensive response to orthostatic stress in patients with systolic hypertension after long-term thiazide diuretic therapy.

Estimation of left and right ventricular filling pressures after heart transplantation by tissue Doppler imaging.

Current Doppler methods have been unreliable in estimating filling pressures in heart transplants. Tissue Doppler imaging is a technique that permits evaluation of myocardial relaxation; combined with transvalvular E velocity, it could improve estimation of these pressures. To investigate this possibility, we evaluated 50 patients by right-sided cardiac catheterization and Doppler echocardiography simultaneously. Their mean +/-SD age was 53+/-15 years and the mean age of donor hearts was 30+/-12.5 years. The mitral E velocity was combined with the early myocardial relaxation (Ea) velocity by tissue Doppler at the lateral border of the mitral annulus. Likewise, the tricuspid E velocity was combined with Ea at the lateral corner of the tricuspid annulus. Mean wedge pressure related weakly to mitral inflow variables but strongly to E/Ea [r=0.8; wedge pressure=2.6+1.46(E/Ea)]. In 25 repeat right-sided cardiac catheterizations, changes in mean wedge pressure were well detected by Doppler, with a mean difference of -0.7+/-3 mm Hg. Mean right atrial pressure related weakly to routine tricuspid inflow variables but strongly to tricuspid E/Ea [r=0.79; n=38; right atrial pressure=1.76(E/Ea) - 3.7]. In 18 repeat right-sided cardiac catheterizations, changes in mean right atrial pressure were well detected by Doppler, with a mean difference of 0+/-3.45 mm Hg. Mean wedge pressure and mean right atrial pressure can be estimated in heart transplants with reasonable accuracy using the ratio of E/Ea. Furthermore, this method can accurately track changes in filling pressures.

Captopril administered every three hours in difficult-to-control hypertension.

The renovascular hypertension of an elderly patient, which was controlled initially with standard-dose therapy with captopril, later responded only to 75 mg given every 3 h without side effects. Changeover to another class of antihypertensives, as is recommended in recalcitrant cases, was not needed. Convenient maintenance therapy with lisinopril (10 mg twice daily) has kept blood pressure under control for a year.

Arterial oxygenation and pulmonary function with Saralasin in chronic lung disease.

During our earlier saralasin infusion study in hypertensive patients, we found a drug-induced rise in arterial oxygen tension (PaO2) associated with unchanged mixed venous PO2 or the PaCO2 and unrelated to cardiopulmonary hemodynamic changes. To test the hypothesis that saralasin improved pulmonary mechanics, blood gases, lung mechanics, lung volumes, diffusing capacity, and distribution of ventilation were analyzed and cardiac output (CO) measured in 12 normotensive men with chronic pulmonary disease before and during a 2 1/2 hour infusion of Saralasin (5 micrograms/kg/min). The PaO2 increased from a mean of 63 +/- 3 (SEM) to 70 +/- 3 mm Hg (p less than 0.001), while the CO decreased from 6.81 +/- 0.52 L/min to 6.18 +/- 0.48 L/min (p less than 0.005). The change in (delta)CO correlated with delta PaO2 (r = -0.67, p less than 0.05). Total systemic vascular resistance rose from 1,201 +/- 134 to 1,353 +/- 147 dynes X sec X cm5 (p less than 0.001). The PaCO2 and other measurements remained unchanged. We conclude that saralasin raised the PaO2 not by changing pulmonary function or mechanics, but by redistributing pulmonary blood flow and improving the ventilation-perfusion relationship.

Clinical efficacy and cost comparison of an amiloride-hydrochlorothiazide combination versus hydrochlorothiazide and wax-matrix potassium supplement in the treatment of essential hypertension.

To compare the clinical efficacy and cost of therapy with an amiloride-hydrochlorothiazide combination versus hydrochlorothiazide and a wax-matrix potassium supplement, we reviewed the medical records of 20 hypertensive men who had received both treatments. The review period included 5.9 +/- 0.9 (mean +/- SE) months on hydrochlorothiazide and wax-matrix potassium and 5.3 +/- 0.7 months after changeover to the amiloride-hydrochlorothiazide combination. Control of blood pressure, maintenance of serum potassium levels, and number of outpatient visits were similar before and after the change in therapy. The monthly cost of medication, based on the lowest listed price in the Drug Topics Red Book and also in the Red Book Update, was approximately 12% higher for the hydrochlorothiazide and wax-matrix potassium regimen than for the amiloride-hydrochlorothiazide combination, whereas the federal agency contract price for the latter was significantly higher. The change to the amiloride-hydrochlorothiazide combination reduced the mean number of tablets taken daily from 5.3 +/- 0.6 to 1.25 +/- 0.1, suggesting a more convenient therapeutic regimen.

Factors encouraging research productivity in a division of general internal medicine.

The authors investigated two of the causes of and possible remedies for low research activity (as measured by rate of publication) of faculty members in a division of general internal medicine at a university hospital and its affiliated Veterans Administration medical center. They did this by analyzing information about the faculty in the health center's records spanning a 16-year period. This 1989 study suggests that the general medicine faculty members who are also involved in subspecialties and who have protected research time can improve their research productivity.

Hormonal response to orthostasis in elderly people with systemic systolic hypertension.

BACKGROUND: Orthostatic hypotension is a common phenomenon in the elderly. Hormonal changes during orthostatic stress have been described in elderly normotensive people and in those with essential hypertension. However, the hormonal response in elderly people who have systolic hypertension during orthostasis has not yet been quantified. METHODS: In this study we investigated 14 non-diabetic men, aged 60 to 75 years, with untreated systolic hypertension who were subjected to 45 degrees passive head-up incline on a tilt table for 15 min. Their hormonal profile and hemodynamic changes were analyzed before and after the stress. RESULTS: In the supine position, plasma levels of norepinephrine, atrial natriuretic peptide and aldosterone were in the normal range, while the plasma renin activity was low. Immediately upon tilt the systolic blood pressure fell but it reverted to baseline values after 15 min of orthostasis. At that time the cardiac output decreased while the systemic vascular resistance and the plasma norepinephrine concentration rose. The atrial natriuretic peptide appeared to fall, and the renin-aldosterone level did not change. CONCLUSION: The physiologic response to orthostatic stress in elderly people with systolic hypertension is comparable to that of elderly normotensive people and those with essential hypertension, i.e. a decrease in cardiac output and an increase in plasma norepinephrine levels. The atrial natriuretic peptide appeared to fall appropriately. The response of the renin-aldosterone system mimicked that in elderly patients with low renin essential isolated hypertension. These observations may have a bearing on the management of elderly people with systolic hypertension who also have orthostatic symptoms; they may not require a different approach from that needed for others of the same age group.

Case report. Acute cor pulmonale due to massive pulmonary embolism and successful response to thrombolytic therapy.

The proper place of thrombolytic agents in the management of pulmonary embolism is not yet well defined. A number of survivors of acute massive pulmonary thromboembolism remain in a delicate balance of hemodynamic compensation and where recurrent emboli could frequently be fatal. Successful response to urokinase therapy in such a case is presented and the status of currently available thrombolytic drugs is discussed. We suggest that thrombolytic therapy in massive pulmonary embolism would provide greater hemodynamic reserve, alleviate shock, minimize the chances of recurrent emboli and prevent permanent impairment to the pulmonary vascular bed.

Case report: spinal cord compression due to metastatic hepatocellular carcinoma.

Hepatocellular carcinoma is an uncommon cancer in the United States. Its initial presentation as spinal cord compression due to vertebral metastasis is rare. This article reports a case of radiculopathy and rapidly developing spinal cord compression because of bony metastasis from this form of liver cancer. This article also reviews pertinent literature and discusses the diagnostic modalities for early detection.

Special features of coronary heart disease in people of the Indian sub-continent.

Contrary to the popular belief, coronary heart disease (CHD) is indeed common in the Indian sub-continent. Expatriate Indians in their newly adopted countries have 3 to 5 times more chance of developing CHD than the native population or the other immigrant groups. The well-known risk factors such as hypercholesterolemia, hypertension and smoking do not appear to play a major role, while the syndrome of insulin resistance seems to be an important risk factor for CHD in people of this sub-continent. Abdominal obesity, hypertriglyceridemia, and low plasma HDL cholesterol are the markers of this syndrome. Increased plasma insulin levels or even better, the C-peptide measurement may help in identifying the abnormality early. As CHD among Indians has been found to be severe and more diffuse with serious complications and increased mortality at a younger age, preventive measures need to be instituted early. Low fat and complex carbohydrate diet along with regular aerobic exercise may help reduce abdominal obesity, improve insulin sensitivity and HDL cholesterol levels. Hypertriglyceridemia uncontrolled by above measures may require pharmacotherapy with agents such as gemfibrozil. Smoking must be stopped to help reduce insulin resistance and improve HDL levels and endothelial function. Those with hypertension should be considered for therapy with ACE inhibitors, which may improve insulin sensitivity. In patients with insulin resistance, therapy with metformin or troglitazone may be helpful.