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Biomedical subjects

J M Nicklas

Publications and source records attributed to J M Nicklas.

At least 37 records · Page 2Linked to original sources
PubMed1989

Natriuresis associated with elevated plasma atrial natriuretic hormone during supraventricular tachycardia.

Elevated plasma levels of atrial natriuretic hormone (ANH) have been found in patients during paroxysmal supraventricular tachycardia (SVT) and other clinical syndromes. However, physiologic effects of this endogenous ANH have not been demonstrated. To determine whether the rise in ANH during SVT is associated with either a natriuresis or kaliuresis, urine sodium and potassium levels were measured in five patients at baseline and during SVT simulated by rapid atrioventricular pacing. Plasma ANH levels increased from 149 +/- 35 pmol/L at baseline to 187 +/- 31 pmol/L (p = 0.007) during SVT. Plasma vasopressin and renin levels were unchanged. Urine sodium levels increased 49% from 1.54 +/- 0.66 mEq/hr at baseline to 2.29 +/- 0.89 mEq/hr (p = 0.044) during SVT, and urine potassium levels increased 22% from 4.14 +/- 0.10 mEq/hr to 5.04 +/- 1.25 mEq/hr (p = 0.018). Urine sodium and potassium levels returned to baseline values 1 hour after pacing. Thus elevated plasma levels of ANH during SVT are associated with both a natriuresis and kaliuresis, which may represent physiologic effects of the endogenously secreted hormone.

Atrial Natriuretic Factor↗
PubMed1989

Amrinone versus conventional therapy in pulmonary hypertensive patients awaiting cardiac transplantation.

Pulmonary hypertension is associated with an increased perioperative mortality for orthotopic heart transplantation. A transpulmonary gradient greater than 15 mm Hg or a pulmonary vascular resistance greater than 5 Woods units increases mortality secondary to right heart failure. This study compares amrinone with conventional therapy in 38 transplant candidates with pulmonary hypertension. All patients had elevated transpulmonary gradient, pulmonary vascular resistance, or both. Group 1 (n = 21) received prolonged continuous intravenous amrinone therapy, whereas group 2 (n = 16) received high-dose oral diuretics, digitalis, and captopril. Both groups 1 and 2 had decreased pulmonary hypertension, transpulmonary gradient, and pulmonary vascular resistance. However, amrinone was more effective, with a 86% response rate versus 63% response for conventional therapy. Survival awaiting transplantation was significantly higher in group 1 (20 of 22, 91%) than in group 2 (10 of 16, 63%). Although both groups 1 and 2 had significantly decreased pulmonary vascular resistance, only group 2 had significantly decreased systemic vascular resistance. Comparison of pulmonary vascular resistance after therapy showed that the response in group 1 (amrinone) was significantly lower than the response in group 2 (conventional therapy), suggesting that amrinone may function as a direct vasodilator of the pulmonary vasculature. There were no operative deaths or episodes of perioperative right heart failure in either group. Amrinone appears to be more effective and safe than conventional therapy in the treatment of prospective heart transplant candidates with pulmonary hypertension.

Adult↗
PubMed1989

An algorithm for the quantification of ST-T segment variability.

A template boundary algorithm which quantitatively determines repolarization (ST-T segment) variability in a normal population has been developed. The algorithm defines an initial ST-T template for comparison with successive beats. Variability is quantified using boundary limits around the template which are widened, when necessary, to included incoming ST-T segments. The boundaries at the end of each hour are stored and the collection of boundaries over a set of normal subjects quantifies the normal variation over the entire ST-T segment. The algorithm can be used to determine prospectively normal ST-T variability based on a regression analysis of R-wave or T-wave amplitude, and QT interval. Application of these boundary predictions should be useful in distinguishing repolarization changes secondary to ischemia from normal variability.

Algorithms↗
PubMed1989

Randomized, double-blind, placebo-controlled trial of tissue plasminogen activator in unstable angina.

Angiographic, angioscopic and pathologic reports have recently demonstrated a high incidence of intracoronary thrombus in patients with unstable angina. To determine if thrombolysis could be beneficial when combined with maximal medical therapy, 40 patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia were randomly assigned to intravenous recombinant tissue-type plasminogen activator (rt-PA, 150 mg/8 h) or placebo in a prospective double-blind trial. All patients received nitrates, a beta-adrenergic blocking agent, a calcium channel blocker, aspirin and heparin. Pacing thresholds for ischemia and quantitative coronary stenosis were measured before and after infusion of the study medication. Intracoronary thrombus was identified angiographically before infusion of the study medication in 16 patients; 7 received rt-PA and 9 received placebo. The ischemic pacing threshold in patients treated with rt-PA increased from 112 +/- 4 beats/min at baseline to 127 +/- 5 beats/min (p = 0.007) by the end of the infusion versus an insignificant change in patients who received placebo (from 116 +/- 4 to 119 +/- 4 beats/min, p = NS). In patients with intracoronary thrombus, the ischemic pacing threshold increased 26 +/- 7 beats/min with rt-PA treatment versus 0 +/- 3 beats/min with placebo (p = 0.004). In contrast, in patients without thrombus, there was no difference in ischemic pacing threshold increments between treatment groups (7 +/- 11 beats/min for rt-PA versus 6 +/- 5 beats/min for placebo, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Decreased coronary flow reserve after transient myocardial ischemia in dogs.

The effect of a transient (15 min) period of regional ischemia on coronary flow reserve in the postischemic myocardium was studied in 24 open chest dogs. Coronary flow was measured with electromagnetic flow probes, and flow reserve was determined during reactive hyperemia after 30 s coronary occlusions and during intracoronary infusions of adenosine. Measures of flow reserve after 15 min of ischemia were made after coronary flow returned to basal levels and flow reserve was then monitored for 1 h. All measures of coronary flow reserve were significantly reduced after transient ischemia: peak flows during reactive hyperemia and intracoronary adenosine infusions decreased by 20 and 24%, respectively, the peak/basal flow ratio by 16% and the repayment/debt ratio by 54%; minimal coronary vascular resistance during reactive hyperemia and intracoronary adenosine increased by 29 and 33%, respectively. Abnormal flow reserve was present for at least 1 h. No changes in flow reserve were detected in control animals over the same time period. Thus, a transient period of myocardial ischemia significantly decreases coronary flow reserve for a prolonged period of time. This "vascular stunning" must be considered when flow reserve is used to assess the functional significance of a coronary stenosis and could be the cause of variable exercise tolerance in patients with angina pectoris.

Animals↗
PubMed1988

Coronary revascularization after intravenous tissue plasminogen activator for unstable angina pectoris: results of a randomized, double-blind, placebo-controlled trial.

To determine the role of intravenous tissue plasminogen activator (t-PA) in unstable angina, it was compared with placebo in a randomized, double-blind trial. Forty patients with angina at rest and provocable ischemia (pacing induced) had baseline coronary angiography, study drug infusion and then repeat angiography at 20 +/- 9 hours. All patients received diltiazem, nitrates, beta blockers, aspirin and intravenous heparin. During study drug infusion (150 mg over 8 hours), refractory ischemia necessitating emergency bypass surgery (CABG) or coronary angioplasty (PTCA) occurred in 4 of 20 t-PA patients compared with 1 of 20 placebo patients (p = 0.21). Before discharge, revascularization for persistent, provocable ischemia and a residual stenosis greater than or equal to 60% was as follows: t-PA patients, 8 PTCA and 7 CABG; placebo patients, 11 PTCA and 8 CABG (p = 0.39). Quantitative angiographic percent diameter stenosis of the culprit artery at baseline and follow-up was: t-PA 71 +/- 17 and 63 +/- 22; placebo 70 +/- 19 and 67 +/- 22 (difference not significant). However, 3 t-PA patients compared with no placebo patients demonstrated an insignificant (less than 60% diameter) residual stenosis and averted PTCA (p = 0.14). There were no complications of PTCA in the 8 t-PA patients; in contrast, 3 of 11 placebo patients had abrupt closure, necessitating emergency CABG in 2 (p = 0.23). Thus, intravenous t-PA in unstable angina can eliminate the need for PTCA in a few patients, does not appear to decrease the overall or emergency rate of revascularization procedures and may facilitate the safety of PTCA.

Angina Pectoris↗
PubMed1988

Kinetics, dynamics, and bioavailability of bumetanide in healthy subjects and patients with congestive heart failure.

Four healthy subjects and six patients with congestive heart failure (CHF) were given 3 mg oral and intravenous doses of bumetanide in a random crossover fashion. Bumetanide was analyzed by HPLC, and sodium and potassium was analyzed by flame photometry. Aside from a modest reduction in renal clearance, the kinetics of bumetanide in CHF were similar to those in healthy subjects. The extent of bioavailability was 81%, with a variability of 20% to 25% about the mean for both groups. The cumulative dynamic responses to bumetanide, whether administered orally or intravenously, were essentially the same in each group. Pharmacodynamic modeling showed that there were no significant differences between healthy subjects and patients with CHF in either ER50 (bumetanide urinary excretion rate producing 50% of maximum drug effect) or S (slope), although the baseline effect was 15 times lower in CHF. The maximum effect attributable to bumetanide was twofold higher in healthy subjects and there was a significant correlation between this parameter and creatinine clearance (r = 0.964; p less than 0.001). Overall, these results indicate that a predictable transition from 3 mg intravenous to oral doses of bumetanide is possible in CHF.

Administration, Oral↗
PubMed1987

Exercise testing three days after onset of acute myocardial infarction.

To determine the feasibility and predictive value of early exercise testing 72 hours after acute myocardial infarction, 109 consecutive patients who received reperfusion therapy were prospectively evaluated. In the group studied, in 87 (80%) the course was uncomplicated 3 days after admission, as defined by a lack of congestive heart failure, arrhythmias and angina, and 53 patients (49%) performed heart rate-limited (140 beats/min) treadmill exercise. These patients exercised for 7.9 +/- 3.4 minutes, achieving a heart rate of 129 +/- 11 beats/min and a systolic blood pressure of 151 +/- 27 mm Hg. The exercise test was not accompanied by any protracted ischemia, infarction or significant arrhythmias. Accompanying tomographic thallium-201 scintigraphy demonstrated a reversible perfusion defect in 14 patients (26%), no evidence for ischemia in 36 patients (69%) and an equivocal result in 3 patients (6%). Of the 14 patients with a positive exercise-thallium test result, 4 had an adverse clinical outcome of either reinfarction, postinfarction angina or ventricular tachycardia during hospital days 4 to 10; an adverse in-hospital outcome was not seen in the 40 patients with a negative exercise-thallium test result (p = 0.009). Thus, early exercise testing after acute myocardial infarction is safe in selected patients with an uncomplicated course and the test is predictive of in-hospital clinical outcomes.

Adult↗
PubMed1987

Quantitative measurement of coronary flow during medical revascularization (thrombolysis or angioplasty) in patients with acute infarction.

This study quantitatively evaluated the change in myocardial blood flow resulting from medical revascularization in patients with acute anterior myocardial infarction. Changes in great cardiac vein flow were measured using a thermodilution technique in 13 patients with acute infarction; 3 received intracoronary streptokinase and 10 percutaneous transluminal angioplasty. Average great cardiac vein flow during left anterior descending coronary artery occlusion was 62 +/- 6 ml/min and increased to 70 +/- 7 ml/min (p = 0.039) after arterial recanalization. There was significant individual variability in the great cardiac vein flow increments that was highly predictive of functional recovery as expressed by the change in ejection fraction at 7 to 10 days (r = 0.93, p = 0.0008). Incremental great cardiac vein flow was inversely correlated with the degree of residual stenosis and the duration of ischemia (r = 0.88, p = 0.0007). Patients with residual stenosis less than or equal to 50% had a significantly larger increase in great cardiac vein flow (14 +/- 5 ml/min) than did those with residual stenosis greater than 50% (0 +/- 2 ml/min, p = 0.026). Neither preinterventional left ventricular ejection fraction, hemodynamics nor age predicted incremental great cardiac vein flow. Therefore, quantitative measurements of great cardiac vein flow during medical revascularization in patients with an acute anterior myocardial infarction demonstrate variable reflow that is physiologically significant. A high grade residual stenosis and prolonged period of ischemia limit large increases in flow and prevent functional recovery. This study emphasizes the fact that recanalization in itself cannot be used as an indicator of the success of interventions designed to produce myocardial reperfusion.

Acute Disease↗
PubMed1987

Development of a template boundary algorithm to determine the ST-T threshold for silent ischemia.

A template boundary algorithm which quantitatively determines ST-T variability has been implemented and tested using seven normal patients. Relatively uniform variability was demonstrated throughout the ST-T segment in these patients during single lead continuous electrocardiographic monitoring at bedrest. The range of variability appears to be a function of both R wave and T wave amplitude. This algorithm appears to have potential utility in defining the ischemic criteria for silent ischemia.

Algorithms↗
PubMed1986

Interrelationships between serum levels of amiodarone, desethylamiodarone, reverse T3 and the QT interval during long-term amiodarone treatment.

The interrelationships between serum levels of amiodarone, desethylamiodarone, and reverse T3, and changes in the corrected QT interval (delta QTc) were examined in 22 patients during long-term treatment with amiodarone. At 1, 3, and 6 months of follow-up, the correlation coefficient between serum levels of amiodarone or desethylamiodarone and reverse T3 ranged from 0.01 to -0.2 (p greater than 0.4). At the same time intervals, the correlation coefficient between both amiodarone and desethylamiodarone levels and delta QTc ranged from 0.1 to -0.1 (p greater than 0.6), and the correlation coefficient between reverse T3 and delta QTc also ranged between 0.1 to -0.1 (p greater than 0.5). Substituting percent delta QTc for delta QTc also did not reveal a significant correlation. These data demonstrate that serum levels of reverse T3 cannot be used as a substitute for serum levels of amiodarone in monitoring patients being treated with amiodarone. The absence of a correlation between serum reverse T3 levels and delta QTc suggests that the delay in repolarization which occurs during amiodarone therapy is not secondary to an amiodarone-induced abnormality in thyroid hormone metabolism.

Adult↗
PubMed1986

Effect of programmed ventricular stimulation on myocardial lactate extraction in patients with and without coronary artery disease.

The arterial-coronary sinus lactate difference was measured in 17 patients after each step of a programmed ventricular stimulation protocol consisting of single, double, and triple extrastimuli, first at a basic drive cycle length of 600 msec, then at 400 msec, with an inter-train interval of 4 seconds. Four patients had no structural heart disease, four had an idiopathic dilated cardiomyopathy, and nine had coronary artery disease with a significant stenosis in at least one branch of the left coronary artery. Net myocardial lactate production during programmed ventricular stimulation was observed in three patients with coronary artery disease, but not in any patient without coronary artery disease. Among the patients who had coronary artery disease, net myocardial lactate production generally occurred in the patients who had more severe coronary artery disease. Exercise-induced ischemia, as demonstrated by a stress thallium-201 test, did not correlate with myocardial lactate production during programmed ventricular stimulation. Programmed ventricular stimulation, with a stimulation protocol typically used in many electrophysiology laboratories, is capable of inducing myocardial ischemia in at least some patients who have coronary artery disease. This finding suggests that myocardial ischemia may potentially influence the results of programmed ventricular stimulation in some patients with coronary artery disease.

Adult↗
PubMed1986

Plasma levels of immunoreactive atrial natriuretic factor increase during supraventricular tachycardia.

A significant diuretic and natriuretic response occurs during paroxysmal supraventricular tachycardia (SVT). Although the diuresis may be secondary to suppression of vasopressin secretion, the etiology of the natriuresis remains unexplained. To determine if atrial natriuretic factor (ANF) could contribute to the polyuric response during SVT, 10 patients were studied: five during spontaneous SVT and five during simulated SVT produced by rapid simultaneous atrial and ventricular pacing. Plasma immunoreactive ANF (IR-ANF) levels measured by radioimmunoassay were obtained at baseline (before and/or 24 to 48 hours after SVT) and after at least 15 minutes of SVT in all patients. During spontaneous and simulated SVT, IR-ANF was significantly elevated (mean +/- SE; 275 +/- 68 pmol/L) compared to baseline (28 +/- 7 pmol/L; p = 0.0036). Similar increases in IR-ANF were noted during both simulated and spontaneous SVT. To determine if this IR-ANF release was related to the increase in heart rate or the rise in right atrial pressure during SVT, IR-ANF levels were also measured in five patients with sinus tachycardia and in six patients with congestive heart failure. IR-ANF was significantly related to right atrial pressure (r = 0.93; p = 0.0009) but not to heart rate (r = 0.46). Thus, IR-ANF is elevated during SVT and may contribute to the natriuretic response. The stimulus to IR-ANF secretion during SVT appears to be related to the rise in right atrial pressure rather than to the increase in heart rate.

Adult↗
PubMed1986

Prediction of left ventricular ejection fraction using simple quantitative clinical information.

The left ventricular ejection fraction is useful in characterizing cardiac performance and evaluating prognosis in patients with known or suspected cardiac disease. The purpose of this study was to determine if simple, quantitative clinical information generated as part of a routine patient evaluation could be used to predict ejection fraction determined by radionuclide ventriculography. Multiple regression analysis was used to study a group of 64 patients selected to represent the full range of ejection fraction values. All patients had undergone cardiac catheterization and standard chest radiography in addition to resting and exercise radionuclide ventriculography. Using easily determined clinical variables, a regression formula was developed that predicted the radionuclide ventriculographic ejection fraction (r = 0.73). Plain film heart volume, heart rate, pulse pressure, and thoracic width were highly significant terms in the optimal regression equation. For validation, the formula was applied to a second, independent verification data set composed of 41 cases and revealed similar correlation (r = 0.78). A radionuclide ventriculographic ejection fraction below 40 was identified in the verification data set with a sensitivity of 87 percent and specificity of 83 percent. Use of this method, requiring only direct heart rate, blood pressure, and chest radiographic measurements and simple calculations, may assist physicians in patient management and facilitate the optimal use of more invasive and expensive studies.

Blood Pressure↗