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Biomedical subjects

M A Fitzpatrick

Publications and source records attributed to M A Fitzpatrick.

52 records · Page 3Linked to original sources
PubMed1988

Atrial natriuretic hormone has biological effects in man at physiological plasma concentrations.

Whether atrial natriuretic hormone (ANH) has biological effects at physiological plasma levels in man is not known. Accordingly, we investigated the effects of a 3-h low dose infusion of human ANF (0.75 pmol/kg.min; i.e. 0.0023 micrograms/kg.min) in six normal men, whose sodium intake was normal while sitting, in a single blind, random order, placebo-controlled study. The ANF infusions induced changes in plasma ANH concentrations entirely within the range for normal subjects. The small increases in plasma ANH values were associated with a significant rise in urinary excretion of sodium, magnesium, calcium, and cGMP. PRA and plasma aldosterone concentrations uniformly decreased to 50% and 64% of placebo values, respectively. Systolic and mean arterial pressures fell significantly from preinfusion values during the ANH infusions. These findings constitute strong evidence that ANH is a hormone of physiological significance in the regulation of body fluid volumes in normal man.

Adult↗
PubMed1987

Research utility of noninvasive methods for measurement of cardiac output.

Two noninvasive methods of cardiac index (Q) determination, pulsed Doppler echocardiography (QDop), and CO2 rebreathing (QCO2) were compared to dye dilution in eight normal volunteers. Measurements of Q were made by dye dilution (QDD) and the two noninvasive techniques under the following conditions: supine rest, after inflation of cuffs around the thighs, 35-degree head-up tilt, supine rest repeated, during constant isoproterenol infusion, and after an intravenous bolus of propranolol. When mean Q values of the group for each intervention were compared, close agreement was observed between dye dilution and each noninvasive method (QDOP = 1.08 QDD - 0.07 L/min X m2, r = 0.99, SEE = 0.02; QCO2 = 0.68 QDD + 0.84 L/min X m2, r = 0.97, SEE = 0.02). Fair correlations were achieved when all 48 paired observations were analyzed (QDop = 1.00 QDD + 0.17 L/min X m2, r = 0.89, SEE = 0.17; QCO2 = 0.71 QDD + 0.77 L/min X m2, r = 0.79, SEE = 0.20). However, the Doppler ultrasound technique was significantly more precise in quantitating changes in Q in individual patients. These results demonstrate that estimates of Q can be made with reasonable accuracy by either CO2 rebreathing or Doppler echocardiography. However, the Doppler technique is a much more accurate means of quantitating acute changes in Q.

Adult↗
PubMed1987

Red blood cell Li+-Na+ countertransport, Na+-K+ cotransport, and the hemodynamics of hypertension.

Red blood cell Li+-Na+ countertransport and Na+-K+ cotransport activities, home blood pressure, invasive systemic hemodynamics, and limb venous compliance were measured in 65 white men (23 normotensive, 22 borderline hypertensive, and 20 mild essential hypertensive subjects). Li+-Na+ countertransport activity was positively and significantly correlated with subject-determined home systolic blood pressure (r = 0.31, p less than 0.02) and with directly measured systolic (r = 0.29, p less than 0.02) and diastolic (r = 0.27, p less than 0.03) blood pressures in the hemodynamic laboratory, independent of potential confounding variables. Analysis of the hemodynamic determinants of blood pressure revealed a significant positive correlation of countertransport with vascular resistance (r = 0.30, p less than 0.02) but not with cardiac output or cardiac index. High red blood cell Na+-K+ cotransport activity was not independently associated with hypertension or with a characteristic hemodynamic pattern but was related to decreased venous compliance. Red blood cell Li+-Na+ countertransport deserves further study as a marker for the genetic substrate of human essential hypertension. Red cell Na+-K+ cotransport may be altered secondarily by factors related to high blood pressure and seems to be a valid marker for abnormalities of the venous system in hypertension.

Adult↗
PubMed1987

The heart and the regulation of renin.

The cause of the low-renin state in hypertension is unknown. To consider our hypothesis that cardiopulmonary mechanoreceptors suppress renin release in these patients, it was necessary to prove that "low pressure" receptors affected renin levels in man. A series of experiments was performed to selectively alter the stretch (load) on carotid and cardiopulmonary baroreceptors in healthy human volunteers. These studies showed that selectively altering high-pressure baroreceptor load did not affect plasma renin activity. Selectively unloading the low-pressure receptors increased plasma renin activity. Simultaneous unloading of both baroreceptors caused the largest increases in renin activity. While the data indicated an interaction of high- and low-pressure receptors on the neural regulation of renin release, we interpreted these results as evidence for a predominant influence of cardiopulmonary mechanoreceptors on the neurogenic regulation of renin secretion in man.

Arteries↗
PubMed1986

Lithium-sodium countertransport: physiological moorings for red cell transport disorders in hypertension.

Erythrocyte lithium-sodium countertransport, a mode of ouabain-insensitive monovalent cation metabolism, is increased in human essential hypertension, but no pathophysiological link to hypertension has yet been established. Similarities between red cell lithium-sodium countertransport and renal proximal tubular sodium-hydrogen ion exchange suggest a possible role for a countertransport analogue in the control of proximal fluid reabsorption. To test this hypothesis, we measured red cell countertransport and renal lithium clearance, a reliable measure of proximal tubular sodium reabsorption, in normotensives and hypertensives. We found that lithium clearance is (a) inversely correlated with red cell countertransport, (b) decreased in essential hypertensives (reflecting increased proximal sodium reabsorption), and (c) lower in normotensive subjects with a family history of hypertension than in those without such a history. The mechanism by which enhanced proximal tubular sodium reabsorption is related to essential hypertension is unknown, but in addition to its connection to lithium clearance, red cell countertransport is correlated with total peripheral resistance and diastolic compliance of the left ventricle. It is therefore possible that alterations of transport demonstrated in red cells reflect generalized membrane characteristics shared by cardiovascular and renal tissues. Measurements of lithium clearance provide a useful tool for further characterizing the control of renal proximal tubular fluid reabsorption in hypertension. Studies using these measurements may help to explain mechanisms of salt sensitivity and differential responses to antihypertensive therapies as well as yield insights into the heritable basis of human hypertension.

Biological Transport, Active↗
PubMed1986

Decreased venous distensibility and reduced renin responsiveness in hypertension.

Abnormalities of renin release and of venous distensibility have been described in essential hypertension. We have postulated that decreased venous distensibility could contribute to the blunted renin response to upright posture in hypertension. Stiffer veins might prevent venous pooling in the lower extremities, which in turn might affect the stretch on cardiopulmonary mechanoreceptors, thereby influencing the reflex release of renin. We investigated this hypothesis in the present study of 47 patients with mild hypertension and 26 (male) healthy volunteers of similar age and race. To induce isolated changes in the stretch of cardiopulmonary mechanoreceptors, systemic hemodynamics were measured before and after thigh cuff inflation at 60 mm Hg for 30 minutes. Cardiac output was determined by dye dilution. Before the intervention, variable thigh cuff pressures were used to measure venous pressure volume with mercury-in-Silastic strain gauge plethysmography. Venous distensibility was diminished in hypertension, as evidenced by a shift in the calf venous volume/pressure curve toward the pressure axis. During the 30-minute experiment, the hypertensive subjects had less blood pooling in their legs in response to thigh cuff inflation, as compared with the control subjects. The hemodynamic and renin responses reflected this diminished effect of thigh cuff inflation on venous return. The smaller increase of renin in the hypertensive group was associated with a smaller fall in the stroke index and right atrial pressure; the reflex rise in the heart rate was also decreased. By pooling blood in the lower extremities, thigh cuff inflation simulates upright posture. It is customary to classify the renin status of hypertensive patients according to the renin response to upright posture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Effect of enalapril on ventricular arrhythmias in congestive heart failure.

Twenty-four-hour Holter electrocardiographic recordings were used to measure the effects of a converting-enzyme inhibitor, enalapril, given for 12 weeks, on the frequency of cardiac arrhythmias in 10 patients with congestive heart failure (New York Heart Association functional class II to III) receiving maintenance therapy with digoxin and furosemide. Nine patients were given placebo, and both study groups were conducted in a double-blind, parallel manner. The placebo group had no change in the frequency of arrhythmias, whereas enalapril-treated patients showed a significant decrease in the frequency of premature ventricular complexes, ventricular couplets and ventricular tachycardia. A minor, nonsignificant reduction in atrial premature complexes was seen in patients who received enalapril. Compared with placebo patients, those who received enalapril had an increase in plasma potassium levels of 0.33 mmol/liter, a decrease in plasma digoxin, and decreases in pulmonary artery wedge, mean pulmonary artery and right atrial pressures. However, none of these indexes were correlated with the concomitant decline in cardiac arrhythmias. It is concluded that enalapril reduces the frequency of ventricular arrhythmias in congestive heart failure, although the underlying mechanisms are not known.

Adult↗
PubMed1985

Hemodynamic effects of angiotensin-converting enzyme inhibitors in essential hypertension: a review.

Angiotensin-converting enzyme inhibitors are vasodilators that exert their beneficial hemodynamic effects in hypertension primarily by withdrawal of the vasoconstricting action of endogenous angiotension II. Although the magnitude of the initial decrease in vascular resistance depends on renin activity, the long-term arterial blood pressure response does not appear to be influenced by initial renin levels. Cardiac output is not significantly altered by angiotensin-converting enzyme inhibition in patients with mild-to-moderate hypertension, but a rise toward normal levels often occurs in patients with severe hypertension or heart failure. Although right and left heart filling pressures are not significantly altered, other evidence suggests that these agents increase venous capacitance. Patients with severe hypertension, for example, have shown increased forearm venous distensibility in response to angiotensin-converting enzyme inhibitors, and a decrease in the ratio of cardiopulmonary blood volume to total blood volume has been demonstrated in normotensive patients with heart failure. Several studies have shown improved renal blood flow after angiotensin-converting enzyme inhibition, suggesting that renal vascular resistance is reduced more than systemic resistance. Reflex tachycardia and other neurohumoral counterregulatory responses occur less frequently than with other vasodilators, because neither the renin-angiotensin-aldosterone nor the autonomic nervous system is activated by angiotensin-converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Effects of enalapril on clinical status, biochemistry, exercise performance and haemodynamics in heart failure.

The effects of enalapril on clinical well-being, treadmill exercise performance, haemodynamic measurements, hormone levels, and plasma biochemistry in patients with moderate heart failure, were assessed in a 12-week placebo-controlled, double-blind study. Maintenance frusemide and digoxin treatment was continued throughout the study. Compared with placebo, enalapril treatment improved clinical status and increased exercise capacity. The most obvious haemodynamic change was a fall in pulmonary artery wedge pressure and pulmonary artery pressure. Enalapril-induced increases in left-ventricular ejection fraction and cardiac index, and falls in systemic arterial pressure, were small. Of the hormone indices measured, plasma renin activity rose 4-fold, angiotensin II and aldosterone fell slightly, and plasma catecholamines were unaltered by enalapril. Plasma potassium increased on average by 0.3 mmol/L during enalapril therapy. No adverse clinical or biochemical effects were observed. Enalapril has a sustained beneficial action in patients with moderate heart failure.

Adult↗
PubMed1984

Enalapril in heart failure.

Serum MK-422 and plasma angiotensin converting enzyme activity were measured during the introduction of enalapril therapy in eight patients with heart failure. In a second study of 16 patients, we recorded exercise tolerance, clinical status and haemodynamics before and after 12 weeks of placebo or enalapril treatment. Increasing doses of enalapril gave step-wise increments in serum MK-422. Plasma converting enzyme activity remained low for at least 24 h after each dose of enalapril (5, 10 and 20 mg). Compared to placebo patients (n = 8), those receiving enalapril (n = 8) tended to improve their exercise performance and clinical status, and showed a fall in right heart pressures after 12 weeks of treatment.

Aged↗
PubMedDate not supplied

Ovine atrial natriuretic factor: sequence of circulating forms and metabolism in plasma.

The sequence of ovine ANF is not known, yet sheep have been used extensively for ANF studies. We sequenced the circulating form of ovine ANF from coronary sinus plasma of sheep in paced heart failure. The main circulating form was identical to human ANF(99-126). Small amounts of ANF identical to human ANF(103-126) and ANF(101-126) peptides were also found. Incubation of labeled ANF in ovine serum suggested ANF(103-126) could be a degradation product of ANF(99-126). The endopeptidase-24.11 degradation product ANF(99-105/106-126) was not found in ovine plasma, in contrast to human plasma where it was a minor component. These results show that while the main circulating forms are similar in sheep and humans, there are differences in the minor peptides.

Amino Acid Sequence↗
PubMedDate not supplied

Stability and inter-relationships of hormone, haemodynamic and electrolyte levels in heart failure in man.

Relationships between clinical status, haemodynamic measurements, hormone and biochemical indices, and maintenance diuretic dose in patients with chronic cardiac failure, are not clear. This study assessed such relationships and their stability under standardized conditions in 21 hospitalized patients. The daily maintenance dose of frusemide correlated closely and in a positive fashion with plasma levels of renin activity, angiotensin II and aldosterone (P less than 0.001), and to a lesser extent with plasma noradrenaline. Although there was some overlap, patients most incapacitated by their heart failure had the highest circulating levels of renin activity, angiotensin II, aldosterone and noradrenaline. Plasma aldosterone correlated closely with concomitant angiotensin II levels (r = 0.70, P less than 0.001) but not with its other secretagogues ACTH (as reflected by plasma cortisol) or plasma potassium. Close positive correlations between angiotensin II and plasma levels of urea and creatinine (P less than 0.01) were observed. Both renin and angiotensin II showed positive relationships with right heart pressures, but were inversely related to cardiac index and arterial pressure. These results show close relationships between clinical and haemodynamic indices on one hand, and hormones on the other. The renin-angiotensin system appears to be the primary regulator of aldosterone under these conditions, and its activity relates closely to haemodynamic measurements and to the degree of azotaemia.

Aged↗
PubMedDate not supplied

Small bowel ischaemia in Fabry's disease.

A patient with previously diagnosed Fabry's disease and a long history of post-prandial abdominal pain died following small bowel infarction. Post-mortem demonstrated Fabry's type deposits in the small vessels and nerves supplying the bowel but in addition, a localized atheromatous stenosis of the superior mesenteric artery. In retrospect, his terminal illness and possibly his chronic symptoms were related to the latter finding. Angioplasty to the superior mesenteric artery may have been of benefit. Mesenteric angiography should be considered in patients with chronic post-prandial pain because large vessel disease may coexist with other a priori pathologies and is imminently treatable.

Arteriosclerosis↗
PubMedDate not supplied

Sharing your culture with a new partner. Catholic system implements plan to integrate values when it acquires a for-profit hospital.

In 1994 Orange County, CA's St. Joseph Health System (SJHS), aiming to strengthen its position in the regional market, acquired Mission Hospital Regional Medical Center, a for-profit hospital believed to be the premier healthcare facility in the southern part of the county. SJHS's leaders began integrating the two cultures at the top, replacing Mission's board but keeping its top managers in place. A member of the Sisters of St. Joseph joined the managers as the hospital's new vice president of sponsorship. In a series of orientation meetings, the hospital's leaders explained SJHS's mission and values to the staff, announcing that Mission would add a pastoral care department, emphasize care of the medically underserved, and discontinue abortion and sterilization procedures. Some Mission staff were disappointed when the hospital terminated a project that offered assisted reproductive technologies. In addition, capitation and exclusive contracting has caused conflict among area physicians, which affects the hospital. And Mission needs to further educate physicians and staff about bioethical issues. On the other hand, Mission has launched a center to help strengthen area families, a transportation system for senior citizens, and a dental clinic for underserved children. It has also taken over sponsorship of a clinic for underserved families. And, in 1994, the hospital opposed Proposition 187, which called for denying state services to illegal immigrants. Many Mission staff have been heartened to learn that the hospital considers justice a core value.

California↗