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Biomedical subjects

W K Laskey

Publications and source records attributed to W K Laskey.

At least 73 records · Page 4Linked to original sources

Arterial wave reflection in heart failure.

Arterial wave reflection may adversely influence both left ventricular afterload and ejection performance. Therefore, using multisensor catheter manometers, we derived wave reflection indexes from ascending aortic pressure and velocity recordings in 17 subjects with clinical heart failure secondary to idiopathic dilated cardiomyopathy and 11 control subjects free of detectable cardiovascular disease. Patients were studied at rest as well as during submaximal supine bicycle exercise. Eight of the subjects with cardiomyopathy were also studied during infusion of nitroprusside at rest and on exercise. Reflection indexes decreased on exercise in normal subjects but did not consistently do so in the subjects with heart failure. In both groups the reflected wave on exercise returned earlier during the ejection period. Infusion of nitroprusside at rest in subjects with heart failure had dramatic, and significant, effects on the magnitude and timing of arterial wave reflections. The effect of nitroprusside on reflection magnitude persisted on exercise, although the timing of the reflected wave was disadvantageous. The systemic arterial response to exercise in heart failure is characterized by a smaller change in wave reflection indexes in spite of a comparable decrease in systemic vascular resistance. Nitroprusside diminishes the potentially adverse impact of wave reflections by decreasing the magnitude of the reflected wave and altering its timing. Additional dose titration studies are necessary to fully assess the benefits of pharmacologic vasodilation during exercise.

Adult↗

Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty.

To test the hypothesis that pretreatment with adequate antiplatelet therapy reduces the likelihood of acute coronary thrombosis during routine percutaneous transluminal coronary angioplasty (PTCA), we reviewed, blinded to treatment group, the films and records of 300 consecutive initially successful PTCAs. Films before PTCA, immediately after, and at least 30 min after the last balloon inflation were assessed for the presence of any thrombus at the PTCA site. We excluded 37 patients who received streptokinase before PTCA or who had 100% occlusion or thrombus on pre-PTCA films. New thrombi were classified as clinically significant (defined as causing 100% occlusion or requiring emergency surgery or streptokinase therapy) or as not significant (not causing an acute problem or requiring intervention). Patients were classified into three groups, based on the type and extent of antiplatelet therapy received. Group 1 (no aspirin, n = 121) consisted of patients who did not receive aspirin either before admission or in hospital before PTCA (with or without dipyridamole). Group 2 (standard treatment, n = 110) received aspirin with or without dipyridamole but did not receive both drugs before admission and in hospital before PTCA. Group 3 (maximal treatment, n = 32) received both aspirin and dipyridamole before admission and in hospital before PTCA. New thrombi were detected at 39 (14.8%) PTCA sites, of which 15 (5.7% of all PTCA sites) were considered clinically significant. Group 1 had the highest incidence of both thrombus (21.5%) and clinically significant thrombus (10.7%). A reduction was seen in group 2 in thrombus (11.8%; p = .07) and in clinically significant thrombus (1.8%; p = .005). Group 3 had no thrombus (p = .001) and no clinically significant thrombus (p = .04). In addition to inadequate pretreatment with antiplatelet therapy, univariate analyses demonstrated several other risk factors for thrombus: higher percent diameter stenosis before PTCA (p less than .008), higher platelet count (p = .013), and current smoking (p = .03). Only higher platelet count (p less than .001) and inadequate pretreatment (p = .001) were associated with clinically significant thrombus. Stepwise logistic regression analysis demonstrated that for thrombus, the lack of effective antiplatelet therapy was the most discriminatory variable, followed by current smoking, higher percent diameter stenosis, and dissection. For clinically significant thrombus, once the lack of pretreatment with effective antiplatelet therapy was considered, no other factors added significant discriminatory information.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Effects of nitroglycerin in patients with angina, normal coronary arteries, and left ventricular hypertrophy.

The coronary hemodynamic and left ventricular mechanical responses to nitroglycerin were studied in eight patients with angina, normal coronary arteries, and pressure overload left ventricular hypertrophy (POLVH) and in five control subjects. Elevated mean and end-diastolic pressure and end-diastolic meridional stress characterized the POLVH group, although systolic meridional stresses were not significantly different from the control group. Thermodilution coronary sinus flow and estimated myocardial oxygen consumption declined significantly following nitroglycerin in both patient groups. Systolic and diastolic mechanical loads also decreased in both groups, although diastolic tone remained elevated in the patients with POLVH. The decrease in coronary sinus flow in the POLVH group was in excess of that expected from the decrease in systolic mechanical load, which suggests a combination of perfusion pressure-dependent decreases in coronary flow as well as an increased resistance to coronary inflow in these patients. The beneficial clinical response to nitroglycerin may reflect the lowered myocardial metabolic demand as well as the decrease in diastolic myocardial tensile and compressive forces.

Adult↗

Effect of high dose aspirin on coronary hemodynamics during pacing-induced myocardial ischemia.

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.

Administration, Oral↗

Characteristics of vascular hydraulic load in patients with heart failure.

Aortic input impedance and hydraulic power were derived from simultaneous catheter recordings of ascending aortic pressure and velocity in eight normal subjects and 11 age-matched subjects with clinical heart failure secondary to idiopathic congestive cardiomyopathy. Resting data revealed the characteristic depression of cardiac output and elevation of systemic vascular resistance in patients with heart failure. The pulsatile component of vascular hydraulic load, characteristic impedance (Zc), was similar in both groups (Zc normal: 85 +/- 30 dyne-sec-cm-5; Zc cardiomyopathy: 93 +/- 33 dyne-sec-cm-5). The oscillatory fraction of aortic input power in patients with heart failure (14 +/- 4%) was also similar to that of normal subjects (11 +/- 2%). The transition from rest to exercise in patients with heart failure was marked by a decrease in the steady component of arterial hydraulic load, although characteristic impedance did not change. A similar qualitative response occurred in normal subjects, although the systemic vascular resistance during exercise remained above normal in patients with heart failure. The modulus of the first harmonic of impedance significantly decreased during exercise in normal subjects but did not change significantly in patients with heart failure. Furthermore, the modulus of the first harmonic of the reflection coefficient decreased significantly during exercise in normal subjects but did not change in patients with heart failure in spite of systemic vasodilation. Exercise appears to impose no additional increase in vascular hydraulic load on the ejecting left ventricle. The similar aortic characteristic impedances in patients with heart failure and in normal subjects, at rest and during exercise, are consistent with a constant oscillatory fraction of input power.

Adult↗

Left ventricular mechanics in dilated cardiomyopathy.

The influence of altered chamber shape on the evaluation of left ventricular (LV) mechanics in idiopathic dilated cardiomyopathy (IDC) is unknown. Nine patients with IDC and 7 subjects with normal LV function were studied with simultaneous LV pressure and M-mode echographic recordings in order to derive LV meridional wall stress. The major axis of the left ventricle, determined from the left ventriculogram at rest, allowed for derivation of circumferential wall stress. The IDC group was characterized by larger end-diastolic and end-systolic LV volumes, increased LV mass, depressed angiographic ejection fraction and more spherical LV chamber shape. Both end-systolic meridional (114 +/- 30 kdyne/cm2) and circumferential (251 +/- 73 kdyne/cm2) wall stresses were elevated in patients with IDC, although the ratio of these stresses was less than normal (2.2 +/- 0.1 vs 2.7 +/- 0.2, respectively). LV load alteration with phenylephrine or nitroglycerin allowed for construction of end-systolic stress-minor-axis dimension and end-systolic stress-minor-axis shortening relations. Similar mean slopes of the meridional end-systolic stress-dimension relation were noted in IDC and normal subjects, although the line was displaced to the right in IDC. The slope of the circumferential end-systolic stress-dimension relation was, however, decreased in patients with IDC. Moreover, the end-systolic stress-fractional minor-axis shortening relation in patients with IDC was displaced downward from the normal relation supporting depressed contractile function in these IDC patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Acute coronary vasoconstrictive effects of cigarette smoking in coronary heart disease.

To investigate the effect of cigarette smoking on the coronary vasculature, coronary sinus flow and myocardial oxygen delivery were measured at rest and during incremental atrial pacing in 10 patients with coronary artery disease. Measurements were then repeated while the patients smoked 2 unfiltered, high-nicotine cigarettes. Although smoking significantly increased the heart rate at rest and double product, coronary sinus flow did not change significantly (141 +/- 32 vs 146 +/- 28 ml/min). At the lowest equivalent pacing rate before and during smoking, the double products were comparable. However, coronary sinus flow was reduced by smoking (146 +/- 28 vs 159 +/- 28 ml/min, p less than 0.01) and coronary vascular resistance was increased (0.96 +/- 0.15 vs 0.83 +/- 0.13 mm Hg ml-1 min, p less than 0.02). The double products were also comparable at the peak pacing rate before and during smoking. Nonetheless, the coronary sinus flow was again lower (167 +/- 23 vs 227 +/- 41 ml/min, p = 0.02) and the coronary vascular resistance was higher (0.77 +/- 0.10 vs 0.63 +/- 0.09 mm Hg ml-1 min, p less than 0.01) during smoking. The transmyocardial arteriovenous oxygen difference was unchanged by smoking; therefore, myocardial oxygen delivery was reduced in proportion to the reductions in coronary sinus flow. Thus, cigarette smoking appears to acutely alter the ability of the coronary vasculature to regulate flow in accordance with the oxygen requirements of the myocardium.

Aged↗

Matching of myocardial oxygen consumption to mechanical load in human left ventricular hypertrophy and dysfunction.

The coupling of myocardial oxygen consumption (MVO2) with its determinants in left ventricular hypertrophy in human beings is poorly understood. Therefore, thermodilution-derived coronary blood flow, MVO2 and left ventricular wall stress, obtained from simultaneous left ventricular M-mode echogram and pressure, were compared in 32 patients with various degrees of left ventricular hypertrophy. Patients were studied at rest and after mechanical load alteration with nitroglycerin or phenylephrine. Decreases in MVO2 (-5.7 +/- 0.8 ml/min; p less than 0.001) and the time integral of meridional ejection stress or shortening load (-1,297 +/- 152 X 10(3) dynes X s/cm2; p less than 0.001) were observed after nitroglycerin administration while increases in MVO2 (+5.5 +/- 0.7 ml/min; p less than 0.001) and shortening load (+1,412 +/- 137 X 10(3) dynes X s/cm2; p less than 0.001) were noted after phenylephrine. An index relating the change in MVO2 to the corresponding change in shortening load (SL), % delta MVO2/% delta SL, was significantly different in patients without (Group 1) and with (Group 2) clinical left ventricular failure. Left ventricular mass was similar in both groups. The mean % delta MVO2/% delta SL with phenylephrine in Group 1 (79.6 +/- 9.6) was greater than the index for Group 2 (35.5 +/- 6.1; p less than 0.005). With nitroglycerin, Group 2 patients exhibited a greater reduction in % delta MVO2/% delta SL (110.5 +/- 17.8) than Group 1 (54.0 +/- 9.4; p less than 0.01). In conclusion, in patients with left ventricular hypertrophy and dysfunction there appears to be a state of diminished coronary flow response to load augmentation. However, load reduction in patients with clinical left ventricular failure results in a more balanced relation between oxygen uptake and ejection stress.

Adult↗

Myocardial energetics and clinical response to the cardiotonic agent MDL 17043 in advanced heart failure.

Cardiotonic agents may prove useful in the long-term treatment of chronic heart failure provided myocardial efficiency is enhanced and clinical status is improved. Accordingly, the short-term hemodynamic and clinical response to the phosphodiesterase inhibitor, MDL 17043, was evaluated. Intravenous increments of 0.05 mg/kg (maximal total 3 mg/kg) were given to a peak cardiac output response in 13 patients with New York Heart Association functional class IV heart failure secondary to ischemic or myopathic disease. Significant (p less than 0.05) responses at peak effect (1.7 mg/kg) included an increase in cardiac output (3.5 to 4.6 liters/min) and heart rate (86 to 90 beats/min) and a decrease in pulmonary capillary wedge (25 to 17 mm Hg), mean arterial (85 to 78 mm Hg) and right atrial (10 to 7 mm Hg) pressures. Coronary sinus flow (measured in nine patients) increased (122 to 144 ml/min, p less than 0.01) as did myocardial oxygen uptake (14.1 to 15.1 ml/min, p less than 0.01), whereas myocardial extraction of oxygen (78 to 72%, p less than 0.01) and lactate (24 to 9%, p less than 0.01) decreased with three patients producing lactate at the time of their peak cardiac output response. Nine of the 12 patients given long-term oral therapy improved at least one functional class at 2 weeks. This improvement was sustained at 20 weeks in five patients. Thus, MDL 17043 acutely improves the function of the failing heart. However, the decrease in oxygen extraction occurring with increased myocardial oxygen uptake suggests that intracoronary shunting may occur along with an increase in oxygen demand and contribute to myocardial anaerobiosis in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanics of pulsus alternans in aortic valve stenosis.

Differences in the mechanics of strong and weak contractions during sustained pulsus alternans were studied in 4 patients with aortic valve stenosis (AS). No significant difference was observed between strong (S) and weak (W) beats in M-mode echographic end-diastolic minor-axis dimension or end-diastolic meridional wall stress. Peak systolic meridional stress (S:225 X 10(3) dynes/cm2; W:205 X 10(3) dynes/cm2), the time integral of left ventricular (LV) meridional systolic stress (S:5,000 X 10(3) dynes/cm2; W:4,500 X 10(3) dynes/cm2) and the area of a stress dimension loop (S:202 X 10(3) dyne/cm; W 165 X 10(3) dyne/cm) were all greater for strong beats. However, end-systolic meridional stress (S:100 X 10(3) dynes/cm2; W:115 X 10(3) dynes/cm2) and end-systolic minor-axis dimension (S:4.75 cm; W:5.0 cm) were significantly greater for weak beats. Stress-length relations, derived from resting and postnitroglycerin determinations, revealed higher end-systolic dimensions for weak beats at any level of limiting afterload, suggesting diminished contractile performance of weak beats. Additionally, fractional minor-axis shortening for weak beats was diminished, at any level of end-systolic stress, in comparison with that for strong beats. The results are supportive of theories suggesting alternating contractile performance during pulsus alternans.

Aortic Valve Stenosis↗

Myocardial oxygen consumption in left ventricular hypertrophy and its relation to left ventricular mechanics.

Alterations in left ventricular (LV) mechanics have significant effects on myocardial oxygen consumption (MVO2) as a result of changing LV pressure and dimensions. However, the effects of load alteration on MVO2 in the setting of LV hypertrophy and LV dysfunction have not been well characterized. Therefore, we examined changes in LV mechanics and MVO2 in 32 patients with varying degrees of LV hypertrophy and LV dysfunction before and after pharmacologic alteration of load. With phenylephrine or nitroglycerin-induced load alteration, changes in peak systolic meridional stress, mean systolic stress and the area of a stress-dimension loop all correlated modestly with changes in MVO2 (r = 0.66, 0.62, 0.63, respectively). However, changes in the time integral of LV ejection stress, or shortening load, were significantly correlated with changes in MVO2 (r = 0.88, p less than 0.001). In particular, load reduction results in a beneficial effect on MVO2. In addition, for a given change in LV systolic pressure, changes in shortening load (38 +/- 3.7%) were significantly greater than changes in tension-time index (13 +/- 1.4%), thus providing a sensitive marker of alteration of mechanical load. We conclude that physiologic alterations in mechanical load in normal persons as well as patients with LV hypertrophy are reflected in significant changes in the time integral of LV ejection stress. These changes in shortening load, mediated by changing LV pressure and dimension, are significantly related to changes in MVO2.

Adult↗

A safe and rapid technique for retrograde catheterization of the left ventricle in aortic stenosis.

The present report describes our experience in 82 patients with a pigtail-straight guide wire system for crossing stenotic aortic valves. The technique was successful in 95% of all the attempts and the average fluoroscopic time was three minutes. There were no major complications of the procedure. The technique allowed for consistent, high quality ventriculograms in 73 patients enabling us to define the severity of concomitant mitral regurgitation in 27 of the patients, as well as a preoperative ejection fraction in all 73 patients. We conclude that the technique as described is a safe and efficient way to obtain both hemodynamic and angiographic information at minimum risk in patients with severe aortic stenosis.

Adult↗

Transseptal left heart catheterization: utility of a sheath technique.

This report describes our experience with a modified sheath transseptal catheter system. The sheath technique allows for introduction of various catheters into the left heart, including a uniquely designed pigtail catheter intended for use with this system. Fifty-three patients underwent successful transseptal catheterization, 44 of whom had severe native aortic valve stenosis and seven with suspected prosthetic aortic valve dysfunction. The technique provides optimal ventriculographic and hemodynamic information as well as improved access to the left heart in patient with aortic valve disease.

Aortic Valve Insufficiency↗

Angiotensin infusion effects on left ventricular function. Assessment in normal subjects and in patients with coronary disease.

Radionuclide multigating of the cardiac cycle was employed to assess effects of angiotensin infusion on left ventricular function. In six normal subjects, angiotensin infusion decreased heart rate (HR) from 72 +/- SEM 2 to 57 +/- 2 beats/min (P less than 0.001); while systolic blood pressure (BP) increased from 119 +/- 2 to 178 +/- 1 mm Hg (P less than 0.001), and ejection fraction (EF) declined from 58 +/- 1 to 47 +/- 2 percent (P less than 0.05). In contrast, in 11 normal subjects, supine exercise increased HR and systolic BP by 55 and 49 percent, whereas EF increased from 64 +/- 1 to 71 +/- 1 (P less than 0.001). In ten patients with CAD, angiotensin infusion produced no change in HR, increased systolic BP by 34 percent, and decreased EF by 11 percent. Angiotensin infusion induced left ventricular depression in normal subjects and in patients with CAD. It cannot substitute for exercise in intervention radionuclide ventriculography.

Adult↗

Blastomycosis in children.

Four cases of blastomycosis in children selected from a larger series of cases seen over 36 months are presented. This infection in the pediatric age group is not often considered in the setting of a slowly resolving pneumonic illness. The morbidity and mortality of this disease in the adult warrant careful consideration of this entity in the pediatric age group, since effective therapy is available.

Adolescent↗