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Biomedical subjects

H G Hanley

Publications and source records attributed to H G Hanley.

At least 19 recordsLinked to original sources

Percutaneous interventions for ischemic heart disease.

In the United States, when necessary due to symptoms or prognosis, percutaneous coronary interventions are performed on patients with ischemic heart disease more frequently than is coronary artery bypass surgery. A wide array of options are available to the interventional cardiologist. Improvements over the 17 years that coronary balloon angioplasty has been performed have kept it the primary therapy. It is currently used safely and effectively in the majority of patients. The problems of abrupt closure, restenosis, and inadequate results in some complex lesions have spurred the development of intracoronary stents, coronary atherectomy and ablation devices, and coronary excimer lasers. Metallic stents perform well in large vessels to treat abrupt closures and to reduce restenosis, but confer a risk of hemorrhage. Specific complexities of lesion characteristics determine the effective use of atherectomy/ablation devices and lasers. Future technologic improvements anticipate even better treatments for patients with coronary artery disease.

Angioplasty, Balloon, Coronary

A rationale for the use of percutaneous transluminal angioplasty in the setting of acute myocardial infarction.

Rapid reperfusion of infarcting myocardium has become a cornerstone of modern medical care. The role of percutaneous transluminal coronary angioplasty (PTCA) in this treatment of acute myocardial infarction is not clear. PTCA is effective in the early hours of MI as primary reperfusion therapy, in lieu of thrombolysis. Arterial patency using this strategy is excellent with low complication rates, and this therapy is comparable and may be superior to thrombolysis when myocardial performance and recurrent ischemia are considered. PTCA is the treatment of choice for the patient in whom thrombolysis is contraindicated, or who develops cardiogenic shock. The role of angioplasty as secondary therapy for myocardial infarction after pharmacologic thrombolysis and reperfusion is controversial. The evidence is clear that immediate PTCA after successful thrombolysis is not warranted. The decision for elective angioplasty after successful or unsuccessful thrombolysis should probably be judged on a case to case basis.

Angioplasty, Balloon, Coronary

Percutaneous transluminal coronary angioplasty: an expanding role in complex coronary artery disease.

Since its inception in 1977, percutaneous transluminal coronary angioplasty (PTCA) has played an increasing role in the treatment of complex single and multivessel coronary artery disease. Many patients, previously treatable only by coronary artery bypass grafting, are now successfully treated with PTCA in the cardiac catheterization laboratory. Two important limitations to the procedure, acute closure and restenosis of the dilated vessels, persist. However, studies with lasers, intracoronary stents, perfusion catheters, thrombolysis, and antiplatelet drugs are ongoing in an attempt to minimize these complications. In addition, studies are now ongoing comparing PTCA with bypass grafting to further define the role of each in coronary disease.

Angioplasty, Balloon, Coronary

Metabolism in human endomyocardial biopsies and cardiac work.

The activities of the Krebs cycle (KC), glycolytic pathway (GP), and the hexose monophosphate shunt were studied in endomyocardial biopsies obtained from 25 patients and were related to left ventricular stroke work index (LVSWI). Unexpectedly, KC activity was greater in patients with a reduced LVSWI than in those with a normal or elevated LVSWI. When the cardiac work:KC ratio, defined as LVSWI divided by KC activity, was plotted against LVSWI, the correlation coefficient was 0.86. Cardiac work did not correlate with other metabolic pathways measured. Patients with a reduced LVSWI generated less cardiac work per unit of KC activity than those who had a normal or elevated LVSWI. These data indicate that a reduction in LVSWI below 40 gram-meters/square meter (gm-m/m2) may be associated with either inefficient energy production, inefficient energy utilization, or both.

Biopsy

Evaluation of a coronary lysing system: results of a preclinical safety and efficacy study.

The purpose of this study was to evaluate the efficacy and safety of a recently developed transluminal lysing system in the removal of coronary stenotic lesions from a human cadaver heart and in the cannulation of coronaries in the anesthetized dog. The left coronary arteries of three dogs were cannulated on separate occasions, with coronary arteriography and translation of the transluminal lysing system cutter to the distal segments of the coronary vessels performed each time. Proximal and distal coronary pressures were recorded from the guiding catheter and the transluminal lysing system cutter, demonstrating no significant pressure differential and minimal damping. Pathological examination of the dog coronaries after sacrifice demonstrated minor intimal irregularities with no significant thrombosis or vessel perforation. A significant portion of the occlusive stenotic lesions were removed from coronary vessels of a human cadaver heart with subsequent reestablishment of angiographic dye flow to the distal coronary vessels without evidence of debris loss from the transluminal lysing system cutter or the appearance of occlusions in the distal vessels. We conclude that the transluminal lysing system can be introduced into the coronary artery of a living dog on repeated occasions without causing significant coronary damage, coronary occlusive thrombosis, myocardial destruction, morbidity, or mortality; furthermore, occlusive stenotic lesions can be removed from cadaver coronary vessels by the transluminal lysing system with the establishment of angiography patency.

Animals

Micromethods for determining activities of energy-producing and non-energy-producing pathways in myocardial tissue.

The increasingly frequent use of endomyocardial biopsies for diagnosis has provided the opportunity to study myocardial metabolism in patients with cardiac diseases. The authors have tested microassays of the hexose monophosphate shunt, glycolytic pathway, and Krebs cycle and demonstrated that they are easily and reproducibly performed on small pieces of cardiac tissue. They have also used these assays to study myocardial metabolism in 2 patients with endocarditis uncomplicated by congestive heart failure and in 2 patients with congestive heart failure due to idiopathic dilated cardiomyopathy. The ability to quantitate myocardial metabolism in biopsies from patients with a variety of cardiac diseases may enhance our understanding of cardiac pathophysiology.

Animals

Reconstruction of the microscopic transmural edge of experimentally infarcted canine myocardium.

Experimental myocardial infarction of the posterolateral left ventricular wall in 2 dog hearts, the result of 1 h of occlusion of the left circumflex coronary artery followed by 4 days of reperfusion, was studied post mortem by serial histological sectioning. Microscopic examination in a transverse plane showed a zone of apparent necrotic muscle removal which formed a continuous boundary between necrotic and normal myocardium without outlying, detached "islands" of necrosis. Reconstruction of the histological transmural edge of infarction at its interface with viable subepicardial muscle demonstrated wide overlapping and angulated interdigitation of the separated tissues across the midzone of the ventricular wall. The observed 3-dimensional spatial complexity of the transmural infarct boundary may be a limiting factor in successful evaluation of this experimentally important region.

Animals

Studies on the mechanism of an antibiotic ionophore, R02-2985 (X537A) in the conscious chronically instrumented dog: involvement of the prostaglandin synthetic pathway.

Conscious dogs were pretreated with a large dose of indomethacin in order to test the hypothesis that prostaglandin synthesis may be involved in the mechanism of action of the inophore R02-2985. The increase in renal blood flow and decrease in renal vascular resistance usually produced by R02-2985 were inhibited by indomethacin. In fact, the calculated renal resistance doubled. In contrast to the effects on renal circulation, indomethacin did not affect coronary blood flow increases which occur independent of contractility changes produced by this ionophore. Effects associated with facilitated release of catecholamines, ie, increases in heart rate, central aortic pressure, and dP/dt were prolonged in comparison to the control study published earlier where these parameters returned to control levels within 2.5 h, thus suggesting that prostaglandin synthesis may somehow potentiate the effects of R02-2985 on the release of catecholamines in vivo.

Animals

Effect of digitalis on estimated splanchnic blood flow.

Digitalis causes vasoconstriction of peripheral vasculature and has been shown to markedly decrease splanchnic blood flow in experimental animals in doses that are comparable to therapeutic doses in man. The effect of digitalis on splanchnic blood flow in heart failure in experimental animals and in man has been controversial. We found that i.v. ouabin reduced ESBF by 30% to 40% (p less than 0.001) in normal volunteer human subjects, that i.v. digoxin reduced ESBF by 15% to 25% (p less than 0.01) in normal subjects, and that oral digoxin had no discernible effect on ESBF in normal subjects. The difference between the effects of i.v. and oral administration appeared to be due to differences in peak blood levels, which were almost 10 times higher after i.v. administration. Glucagon prevented the effect of i.v. digoxin on ESBF in normal subjects. For patients in heart failure, the effect of i.v. digoxin on ESBF was variable: some patients had decreased ESBF but two had increased ESBF that seemed to be associated with a greater increase in cardiac output.

Administration, Oral

Influence of potassium cardioplegia versus ischemic arrest on regional left ventricular diastolic compliance in humans.

To compare the effects of hypothermic ischemic arrest versus hypothermic potassium cardioplegia, regional left ventricular performance was monitored in 20 adult male patients undergoing saphenous vein bypass operation. Twelve patients received ischemic arrest (Group 1), and 8 received potassium cardioplegia (Group 2). Groups 1 and 2 did not differ in left ventricular ejection fraction (0.62 versus 0.60), number of bypassed vessels (3.7 versus 3.4), mean cross-clamp time (75 versus 63 minutes), or mean cardiopulmonary bypass time (182 versus 170 minutes). Before cardiopulmonary bypass was begun, a pair of ultrasonic crystals was secured in the left ventricular anterior myocardium to measure segment motion and a micromanometer-tipped catheter was placed in the left ventricular chamber. All patients received a saphenous vein bypass graft to a vessel supplying the anterior left ventricular wall in the region of the ultrasonic crystals. Comparison of changes in systolic measurements revealed no significant differences between Groups 1 and 2. After saphenous vein bypass grafting, the left ventricular end-diastolic pressure (11.4 to 17.0 mm HG) and modulus of left ventricular segment stiffness (0.37 to 0.67, p less than 0.02) were elevated in Group 1 but no changes were observed in Group 2 (14.0 to 15.6 mm Hg, and 0.16 to 0.24, respectively). Compared with hypothermic ischemic arrest, hypothermic potassium cardioplegia is not associated with an increased left ventricular diastolic stiffness shortly after saphenous vein bypass grafting in humans.

Angina Pectoris

Limitations of postextrasystolic potentiation in identifying ischemic myocardium.

To evaluate the usefulness of postextrasystolic potentiation in differentiating ischemic yet viable myocardium from infarcted myocardium, 20 dogs were chronically instrumented with left ventricular pressure gauges, left circumflex coronary artery flow probes, occluders, pacing wires, and ultrasonic segment-length transducers. Ten dogs had acute (1 h) coronary occlusions followed by reperfusion (4 days) and were then killed. Ten more dogs had more prolonged (1 mo) occlusions and were then killed. Timed premature ventricular contractions were induced, and the postextrasystolic beat was evaluated. In ischemic segments that were hypokinetic, postextrasystolic potentiation of shortening occurred in both groups. In ischemic segments that were akinetic or dyskinetic, potentiation of shortening did not occur in either group. Both groups showed recovery of shortening, and histologically normal myocardium was identified in the region between the segments in all animals. Thus, akinetic and dyskinetic segments did not show postextrasystolic potentiation of shortening, even though the tissue was viable and showed functional recovery. Failure to improve shortening after a premature ventricular beta in an ischemic segment does not necessarily indicate nonviable myocardium.

Action Potentials

Limitations of post-extrasystolic potentiation in assessing regional myocardial viability in man.

UNLABELLED: To investigate the usefulness of regional response to post-extrasystolic potentiation as a predictor of left ventricular viability in patients with coronary artery disease, 46 patients underwent calibrated biplane left ventricular cineangiography during which a single, timed ventricular premature contraction was introduced. RESULTS: Of 758 normal or hypokinetic segments, 486 (64.1%) showed a positive response to post-extrasystolic potentiation. Of 116 akinetic or dyskinetic segments, only 51 (43.9%) showed a positive response to post-extrasystolic potentiation (P less than 0.001). Because akinetic or dyskinetic areas would not be expected to respond to post-extrasystolic potentiation based on animal laboratory data, alternative explanations were sought to explain such positive response in man. Analysis of percent change in chord length of normal or hypokinetic segments adjacent to akinetic or dyskinetic segments that did or did not respond to post-extrasystolic potentiation revealed (10.2% +/- 1.2%) vs (1.3% +/- 0.7%) improvement, respectively (P less than 0.001) (mean +/- SE). CONCLUSION: Passive rather than active events may be responsible for "improved" regional wall motion following post-extrasystolic potentiation in akinetic or dyskinetic regions. If unrecognized, these factors may lead to improper interpretation of "intervention ventriculography" utilizing post-extrasystolic potentiation.

Angiocardiography

Consequences of vasectomy: an immunological and histological study related to subsequent fertility.

Studies of 2 groups of patients 2 years and 8 years following vasectomy failed to demonstrate evidence of cell mediated immunity to sperm. Histological examination of testicular tissue from 11 patients undergoing reversal of vasectomy showed significant abnormalities in each. However, subsequent fertility within 15 months occurred in 7 (63.6%) of these patients. The nature of the testicular changes and the possible aetiological factors are discussed.

Adult

Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog. IV. Energy mechanisms during very early ischemia.

Tissue energy metabolism was examined in posterior (ischemic) and anterior ("control") regions of canine ventricles after 5 and 10 minutes of left circumflex coronary artery occlusion. When compared to identical regions of normal hearts, the following changes were found: (1) decreases in glycogen and phosphorylase activity in the anterior and posterior regions, (2) depressed state 3 rates of oxygen consumption of isolated mitochondria in both anterior and posterior regions, (3) shifts in optimum substrate concentrations for palmityl-CoA (+ carnitine) oxidation by mitochondria in the anterior and posterior regions, and (4) decreases in the apparent zero order and first order rates of mitochondrial palmitylcarnitine production. These changes correlated with a marked decrease in developed tension in the posterior regions. Depression in tension development in the posterior regions of the heart still was present after 30--60 minutes of reperfusion following a 10-minute period of occlusion. Glycogen content in the reperfused areas was significantly decreased after 60 minutes of reperfusion when compared to normal areas and to control hearts perfused for 70 minutes. After reperfusion, mitochondrial function appeared to return toward "normal." However, the slow restoration of contraction of the ischemic area suggests that cellular mechanisms operative in vivo to restore pump function still might be abnormal.

Acyl Coenzyme A