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Biomedical subjects

J M Sullivan

Publications and source records attributed to J M Sullivan.

At least 91 records · Page 5Linked to original sources
PubMed1990

An unusually small potassium current that is well-suited to a retinal neuron which is chronically depolarized.

Here we describe a sustained outward potassium current (IK) in retinal horizontal cells (HCs). IK is unusually small over the range of membrane potentials normally experienced by these cells, which are chronically depolarized. We hypothesize that this unique IK will reduce the amount of neurotransmitter required to shift the cell's membrane potential over a wide range, and will minimize the redistribution of potassium ions across the post-synaptic membrane when the cell is depolarized.

Animals↗
PubMed1990

Clinical and pathophysiologic correlates of ST-T-wave abnormalities in coronary artery disease.

Clinical, hemodynamic and coronary angiographic data from 9,801 patients were evaluated to determine the correlates of ST-segment depression, with or without T-wave inversion, on the resting routine electrocardiogram. The relative risk (RR) of having a measured clinical or angiographic variable was computed whether or not ST-T-wave abnormalities were observed. ST-segment depression was seen significantly more often in subjects greater than 55 years of age (RR = 1.4) who were women (RR = 1.3) or nonwhite (RR = 1.5), were hypertensive (RR = 1.8), had diabetes mellitus (RR = 1.6) or who smoked cigarettes (RR = 1.5). Angiographic findings related to presence of ST-T-wave abnormalities included severe coronary obstruction (less than 70%), higher number of diseased vessels, and the presence of obstruction in the left anterior descending coronary artery. In a multivariate model, the most significant correlates of ST-T-wave abnormalities were presence of left ventricular contraction abnormality, followed by age, gender, presence of left anterior descending coronary artery disease, elevated end-systolic volume index, and a diagnosis of hypertension. Thus, electrocardiographic ST-T abnormalities has specific and significant clinical and pathophysiologic correlates.

Cardiac Catheterization↗
PubMed1990

Unresponsiveness of forearm hemodynamics to omega-3 polyunsaturated fatty acids and aspirin.

Prostaglandin synthesis has been reported to change with aspirin ingestion via cyclooxygenase enzyme inhibition and with marine oil supplementation via an increase in the metabolism of 3-series eicosanoids. This study investigated the effects of pharmacological manipulations of prostaglandin metabolism on forearm hemodynamics and blood pressure. The agents studied were omega-3 fatty acids and aspirin. In the omega-3 fatty acid study, two groups of normal volunteers (N = 10/group) supplemented their diets with either marine oil capsules or placebo. Hemodynamic variables (Mercury-in-Silastic forearm plethysmography) were measured initially and weekly for 4 weeks. There were no significant differences between the two groups in blood pressure, forearm blood flow, venous capacitance, or forearm vascular resistance. Parallel changes occurred for forearm blood flow and venous capacitance. Six normal volunteers took daily dosages of aspirin, increasing from 162 to 2600 mg. Hemodynamic measurements, ADP-induced platelet aggregation, and serum salicylate levels were obtained daily. Maximum inhibition of platelet aggregation occurred after 162 mg. (serum salicylate = 17.7 +/- 6.4 mg/l). Though serum salicylate levels rose to 165.0 +/- 20.0 mg/l, no significant changes occurred in blood pressure or forearm blood flow. Even at aspirin levels 16-fold greater than those required to impair platelet aggregation, the changes in forearm vascular resistance were not found to be significant. These results suggest that under resting conditions in normotensive males, neither pharmacological inhibition nor stimulation of vascular prostaglandin metabolism alters forearm vascular resistance or arterial blood pressure.

Adult↗
PubMed1990

Interactive effects of age and other risk factors on long-term survival after coronary artery surgery.

The effect of age at the time of coronary artery bypass graft surgery on postoperative survival was studied in 2,507 patients with significant coronary artery disease. Patients were subdivided into five groups based on age at the time of surgery: 20 to 39, 40 to 49, 50 to 59, 60 to 69 and greater than or equal to 70 years. The observed death rate was compared with that expected for subjects from the general U.S. population matched for age, gender, race and calendar year. For patients less than or equal to 59 years of age, the ratio of observed to expected death rates was significantly greater than unity (observed/expected = 4.9 for ages 20 to 39, 1.9 for ages 40 to 49 and 1.3 for ages 50 to 59 years, p less than 0.01). The prevalence of risk factors, including diabetes mellitus, hypertension, hypercholesterolemia and cigarette smoking, was evaluated in the different age subgroups. When patients were subdivided on the basis of history of cigarette smoking, the decreased relative survival rate of younger (less than 60 years old) patients existed only in those who smoked (observed/expected = 6.0 for ages 20 to 39, 2.2 for ages 40 to 49 and 1.4 for ages 50 to 59 years). In nonsmokers, observed/expected ratios for every age group were not significantly different from unity. Thus, the reduced relative survival rate of younger patients after coronary artery bypass graft surgery may be attributed to the interactive harmful effects of cigarette smoking.

Adult↗
PubMed1990

Sustained and transient potassium currents of cultured horizontal cells isolated from white bass retina.

1. Horizontal cells (HCs) are second-order neurons in the retina that receive direct photoreceptor input. They rest at around -20 mV in the dark, because of the continuous release of neurotransmitter from photoreceptors. HCs respond to light with graded hyperpolarizations, which can reach -70 to -80 mV in the presence of very bright stimuli. 2. HCs from the retinas of white bass were isolated and maintained in culture. Potassium currents in three morphological types of HCs--H1, H2, and H4--were studied in culture with whole-cell, patch-clamp techniques, when sodium and calcium currents were blocked. 3. A transient outward potassium current (IA), with many characteristics of the A-current, was found in all H2s and H4s but only occasionally in H1s. The threshold for activation of this current was around -40 mV, a value more depolarized than usual for the A-current. The peak IA was typically smaller than 300 pA when the membrane was stepped from a holding potential of -70 mV to a command potential of -10 mV, the upper limit of the in vivo range of HC membrane potentials. Steady-state inactivation is expected to reduce the magnitude of IA in vivo. 4. A sustained outward potassium current (IK) was found in all types of HCs. This sustained potassium current did not activate until the membrane was stepped to potentials above -10 mV, a value much more depolarized than those reported for the delayed rectifier current in other neurons. As a result, IK is absent over the in vivo operating range of these cells. 5. No calcium-dependent potassium current was found in any cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed1990

Comparative effects of propranolol and diltiazem on systolic and diastolic left ventricular function in essential hypertension.

The effects of propranolol and diltiazem on left ventricular systolic and diastolic function in hypertensive subjects (DBP 90-114 mmHg) were examined with M-mode and 2D echocardiograms in 21 patients in a double-blind fashion prior to and after 4 months of treatment. Systolic function was assessed by measurement of fractional shortening, mean velocity of fibre shortening, peak systolic pressure/end systolic dimension ratio, and end systolic stress/end systolic dimension ratio. To assess diastolic function, maximal rate of change in left ventricular dimension (MAXD), maximal rate of change in posterior wall thinning (MAX PWT) and early diastolic (EDD) and late diastolic dimension changes (LDD) were calculated using digitised M-mode images of mid-wall diameter. Both propranolol and diltiazem reduced systolic and diastolic pressures similarly. No significant changes were observed in any of the parameters of systolic function with either drug. Similarly neither propranolol nor diltiazem altered MAXD or EDD significantly. Although changes in maximal rate of posterior wall thinning (MAX PWT) were not significant with either drug, diltiazem improved MAX PWT in 7 of 8 patients. The results of the study demonstrate that both propranolol and diltiazem reduce blood pressure without significant deleterious effects on systolic or diastolic function. Diastolic functional parameters, which were not abnormal at baseline, showed no consistent change with either propranolol or diltiazem.

Blood Pressure↗
PubMed1990

Estrogen replacement and coronary artery disease. Effect on survival in postmenopausal women.

The relationship among postmenopausal estrogen use, coronary stenosis, and survival was examined retrospectively in 2268 women undergoing coronary angiography. The patients were selected for study if their age was 55 years or older at the time of angiography or if they had previously undergone bilateral oophorectomy. Postmenopausal estrogen use in 1178 patients with coronary artery disease (greater than 70% stenosis) and 644 patients with mild to moderate coronary artery disease (5% to 69% stenosis) was compared with 446 control subjects (0% stenosis) using life-table analysis. Over 10 years of follow-up, there was no significant difference in survival among patients initially free of coronary lesions on arteriography who had either never used (377) or ever used (69) estrogens. Among patients with mild to moderate coronary stenosis, 10-year survival of those who had never used estrogens was 85.0% and it was 95.6% among 99 "ever users." Survival was 60.0% among those with more than 70% coronary stenosis who had never used estrogen and it was 97.0% among 70 ever users. The "never users" group were older (65 vs 59 years), had a lower proportion of cigarette smokers (40% vs 57.1%), a higher proportion of subjects with diabetes (21.7% vs 12.9%) and hyperlipidemia (58% vs 44%), and approximately equal numbers of hypertensives (56.0% vs 54.3%). Cox's proportional hazards model was used to estimate survival as a function of multiple covariables. Estrogen use was found to have a significant, independent effect on survival in women. We conclude that estrogen replacement after menopause prolongs survival when coronary artery disease is present, but it has less effect in the absence of coronary artery disease.

Aged↗
PubMed1989

Dose effects of adenine on myocardial ATP content in the post-anoxic nonworking rat heart.

1. Tissue ATP levels were measured in Langendorff perfused nonworking rat hearts subjected to 50 min anoxia prior to reperfusion with Krebs-Ringer bicarbonate (KRB) buffer alone or supplemented with 50 microM or 1 mM adenine for 60 min. 2. ATP content was restored to the normoxic range in hearts reperfused with 50 microM adenine in KRB (20.82 +/- SEM 1.90 mumol/g dry weight vs 24.95 +/- 0.83 in normoxic hearts, P = NS). 3. Reperfusion with oxygenated KRB alone or buffer with 1 mM adenine failed to improve ATP levels (17.23 +/- 0.91 mumol/g dry weight for buffer alone, 15.60 +/- 0.46 with 1 mM adenine and 13.45 +/- 0.93 for anoxic hearts not reperfused). 4. These findings indicate that adenine at 50 microM dosage can restore ATP concentrations to the normoxic range after 60 in of anoxia in the nonworking rat heart while raising the adenine dose to 1 mM inhibited the tissue ATP content.

Adenine↗
PubMed1989

Short- and long-acting angiotensin-converting enzyme inhibitors: a randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. The Multicenter Lisinopril-Captopril Congestive Heart Failure Study Group.

A randomized, parallel, double-blind study was performed with lisinopril, a long-acting angiotensin-converting enzyme inhibitor, versus captopril, a shorter-acting angiotensin-converting enzyme inhibitor, in the treatment of congestive heart failure. All patients were in New York Heart Association class II, III or IV and had remained symptomatic despite therapy with digoxin and diuretics. After a 4 to 14 day placebo baseline period, patients were randomized to receive either lisinopril, 5 mg orally once per day (n = 94), or captopril, 12.5 mg orally three times per day (n = 95), in addition to continuation of digoxin and diuretics. The dose of study drug could be doubled at 4 week intervals for a total of 12 weeks of double-blind therapy. The maximal dose was 20 mg once per day of lisinopril or 50 mg three times per day of captopril. The addition of either lisinopril or captopril to a regimen of diuretics or digoxin, or both, caused an increase in exercise duration as assessed on a motorized treadmill. When protocol violators were excluded, patients receiving lisinopril had a statistically greater increase in exercise duration than that of patients receiving captopril. In patients with renal impairment (serum creatinine greater than 1.6 mg/dl at baseline), lisinopril was superior to captopril in improving exercise duration. Lisinopril, but not captopril, increased left ventricular ejection fraction in patients with moderately to severely (less than 35%) decreased function (p less than 0.05). Improvement in functional capacity and quality of life, as assessed by the Yale Scale dyspnea/fatigue index, was significantly greater for the lisinopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Sodium sensitivity in normotensive and borderline hypertensive humans.

The responses to sodium depletion and repletion were studied in subgroups of 92 normotensive and 65 borderline hypertensive individuals. The borderline hypertensives were characterized by significantly higher blood pressure, weight, cardiac output, hematocrit and decreased density of conjunctival capillaries and venules. Sodium-sensitivity was defined as an increase in mean arterial blood pressure exceeding 5% during sodium repletion. The prevalence of sodium-sensitivity was higher in blacks than in whites and greater in hypertensives than in normotensives. Sodium-sensitive individuals were characterized by significantly increased forearm vascular resistance and decreased plasma renin activity and aldosterone concentration. The resemblance of these changes to those reported in the Dahl salt-sensitive rat suggests a genetic basis for the response to sodium.

Aldosterone↗
PubMed1988

Sodium sensitivity in human subjects. Hemodynamic and hormonal correlates.

To investigate factors associated with sodium sensitivity, 157 subjects were studied while receiving 10 and 200 mEq sodium diets. Measurements included blood pressure (BP), forearm vascular resistance, plasma renin activity (PRA), and plasma aldosterone. Sodium repletion was associated with a greater than 5% increase in mean BP in 16% of the normotensive subjects and 29% of the borderline hypertensive subjects. Sodium-sensitive subjects were compared with sodium-resistant subjects in both the normotensive (n = 92) and borderline hypertensive (n = 65) groups. Forearm vascular resistance was significantly higher (p less than 0.05) during sodium loading in the sodium-sensitive subgroups of both the normotensive and borderline hypertensive groups (35.8 +/- 29 vs 23.8 +/- 20 [SD] and 37.5 +/- 29 vs 22.5 +/- 14 mm Hg/ml/min/100 g, respectively. Venous capacitance was lower in the sodium-sensitive than in the sodium-resistant borderline hypertensive subjects (0.8 +/- 0.21 vs 1.69 +/- 0.24 ml/100 g). During sodium restriction, PRA was significantly lower (p less than 0.01) in the sodium-sensitive subsets (2.56 +/- 1.6 vs 4.04 +/- 2.6; 2.65 +/- 2.1 vs 3.88 +/- 2.6 ng angiotensin I/ml/hr). Aldosterone was lower (p less than 0.01) during sodium depletion in the sodium-sensitive subsets (17.3 +/- 12 vs 26.3 +/- 16; 18.5 +/- 18 vs 27.9 +/- 17 ng/ml). A significant inverse correlation existed between change in BP with sodium repletion and change in PRA or level of PRA during sodium depletion (p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The effect of cigarette smoking on the pattern of coronary atherosclerosis. A case-control study.

Cigarette smoking is a risk factor for development of coronary atherosclerosis. We examined the relationship between smoking and the anatomic location of coronary artery stenosis in 8,705 patients undergoing cardiac catheterization for suspected coronary artery disease (CAD). The smoking history of patients with CAD (greater than or equal to 70 percent stenosis) was compared with that of control subjects (0 percent stenosis) for each of nine anatomic locations (proximal, middle, and distal segments of right [RCA], anterior descending [LAD], and circumflex arteries [LCX]), using a case-control method. The odds ratio (OR) estimate of relative risk of CAD for smokers relative to nonsmokers was 2.8, with a 95 percent confidence interval (CI) of 2.5 to 3.1. Relative risk was greater for RCA stenosis (OR = 5.8; CI = 4.6-7.2) than for LCX (OR = 3.5; CI = 2.7-4.5) or LAD (OR = 2.1; CI = 1.8-2.4) lesions when comparing smokers with nonsmokers. After control for age, gender, history of diabetes mellitus, and serum cholesterol level, the adjusted relative risk for an RCA lesion (Mantel-Haenszel odds ratio [MOR] = 4.9) was significantly elevated (p less than 0.05) compared with the LAD (MOR = 1.9) but not with the LCX (MOR = 3.1). The relative risks of CAD were the same (p greater than 0.05) for the proximal, middle, and distal coronary segments. Thus, smoking increased the risk of all coronary lesions but did so more for the RCA than for other vessels, suggesting a spatial pattern to the increased risk produced by smoking.

Adult↗
PubMed1988

Postmenopausal estrogen use and coronary atherosclerosis.

STUDY OBJECTIVE: To determine whether estrogen replacement therapy affects the prevalence of severely obstructive coronary arterial lesions defined by selective coronary arteriography. DESIGN: Case-control study. SETTING: Large, urban, university-affiliated referral hospital. PATIENTS: From a consecutive sample of 6452 women having coronary arteriography between 1972 and 1984, 2188 patients were eligible for study; others were excluded because they were nonmenopausal, had congenital heart defects, valvular heart disorders, primary myocardial disease, or no more than mild to moderate coronary artery disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospital nurses routinely obtained medication histories. Staff invasive cardiologists interpreted coronary arteriograms. Clinical, laboratory, and angiographic data were abstracted from the cardiac catheterization reports and entered into a computerized registry. Postmenopausal estrogen use for 1444 cases of coronary artery disease (70% stenosis) was compared to that 744 controls (0% stenosis). The odds ratio estimate of the risk of coronary artery disease for estrogen users relative to the risk of coronary artery disease for nonusers was 0.44 (95% confidence interval, 0.29 to 0.67) after adjustment for age, cigarette smoking, diabetes, cholesterol, and hypertension. Postmenopausal estrogen replacement was a significant independent protective factor for coronary artery disease in a multivariate logistic regression model (P = 0.037). CONCLUSION: The data suggest that postmenopausal estrogen treatment reduces the risk for angiographically significant coronary artery disease.

Age Factors↗