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Biomedical subjects

M H Laughlin

Publications and source records attributed to M H Laughlin.

172 records · Page 10Linked to original sources

Increased in blood flow to ischemic myocardium caused by a new dopamine analog.

In the anesthetized, open-chest dog, intravenous infusion 8-13 microgram . kg-1. min-1) of a new dopamine analog 5,6-dihydroxy-2-methylaminotetralin hydrobromide (M-8) demonstrated potent coronary vasodilator properties. Blood flow to normal myocardium was increased an average of 53% above control flow values and this was associated with a decrease in coronary vascular resistance of 50%. The increase in blood flow was distributed uniformly to all portions of the myocardium (left ventricular free wall, right ventricular free wall, and septum). Subendocardial/subepicardial (endo/epi) flow ratios of the left ventricle, right ventricle, and septum were not significantly changed from control. In dog hearts subjected to acute, sudden occlusion of portions of the left anterior branch of the left coronary artery, M-8 produced a 93% increase in flow to the whole heart over postocclusion flow values. Flow to tissues of the heart made ischemic by the occlusive procedure in creased by an average of 94% during M-8 administration despite the fact that the occlusive ligatures remained in place. The vasodilation produced by M-8 was accompanied by a 22-24% increase in myocardial capillary surface area available for exchange of lipid-insoluble substances, fructose and sucrose. Hemodynamic changes associated with M-8 include a transient decrease in aortic pressure, but no change in heart rate, left ventricular (dP/dt)/P, or central venous pressure. Propranolol blocked the vasodilator activity of M-8. It was concluded that M-8 is a beta2-adrenergic receptor agonist having potent coronary vasodilator properties which also has the ability to open preexisting collateral blood flow channels and provide nutritive flow to ischemic, marginally ischemic, and normal myocardium. The cardiovascular actions of M-8 increase blood flow and oxygen delivery to the myocardium while decreasing the work and oxygen utilization by the heart, suggesting that it may have important antianginal characteristics.

Animals↗

Effects of exercise training on coronary reactive hyperemia and blood flow in the dog.

The reactive hyperemic responses to 10-s coronary occlusions were studied in seven sedentary-control (C) and eight exercise-trained (T) anesthetized dogs, with electromagnetic flowmeters placed on the left anterior descending coronary artery. Radiolabeled microspheres (9 +/- 0.8 micron) were used to measure resting coronary flow per gram and to study the effects of isoproterenol infusion (ISO) (1 mg/kg-min) on total and regional coronary flow. Base-line coronary flow per 100 g was significantly greater in the T dogs (122 +/- 7) than in C dogs (100 +/- 4). During ISO, T and C coronary resistances did not differ significantly, whereas the effects of ISO on total and regional coronary flow were quite different in T dogs as compared to C dogs. C and T hyperemic flow debt repayments did not differ significantly; however, the peak reactive hyperemic flow in T dogs (344 +/- 12%) was significantly greater than the control (306 +/- 10%). Since resting coronary flow per gram was greater in T dogs, the greater peak reactive hyperemic flow implies that T dogs have an increased coronary reserve. Although the mechanisms involved are unclear, the results of this study indicate that chronic exercise training may have beneficial effects on coronary physiology.

Animals↗

Use of vectorcardiography for the detection of +Gz-related cardiac pathology in miniature swine.

Vectorcardiograms were recorded from anesthetized, adult miniature swine 1-2 weeks before high sustained +Gz exposure and 2-6 h after exposure. Each +Gz run consisted of one 60-s exposure, respectively, to 3, 5, 7, and 9 +Gz, with 3 min rest between each +Gz plateau. The full range, from severe to minor, of +Gz-induced cardiac pathology was observed in this group of miniature swine. In spite of the large variation in the amount and degree of cardiac pathology, there were no post-exposure vectorcardiographic changes which might be diagnostic of +Gz-induced cardiac pathology. The results of this study indicate that vectorcardiography, performed after +Gz exposure, is not a reliable technique for detecting the presence of +Gz-induced cardiac pathology in miniature swine.

Aerospace Medicine↗

Regional coronary blood flow at rest and during high sustained +Gz in a miniature swine with subclinical, ischemic, coronary heart disease due to coronary stenosis.

New-generation high-performance aircraft can produce levels of high sustained +Gz which may exceed man's physiological capacity to withstand such stress. The severity of this stress has led to concern that sudden incapacitation due to coronary heart disease could occur during sustained +Gz. This report presents results obtained from an apparently asymptomatic miniature swine with a severe stenosis of the left anterior descending branch of the left coronary artery. Regional coronary blood flow was measured with the radiolabeled microsphere technique using 9 +/- 0.8 microgram diameter microspheres. Under resting conditions, myocardial blood flow was marginally depressed in the areas distal to the coronary stenosis. When the animal was exposed to +7 Gz, a large portion of the heart became acutely ischemic due to a redistribution of coronary blood flow. After 49 x of exposure to +7 Gz, the animal developed fatal ventricular fibrillation. Histologically, the areas of myocardium supplied by the stenosed vessel showed a variety of ischemia-induced lesions, including infarction and patchy myocardial fibrosis.

Animals↗

Myocardial transcapillary exchange in the hypertrophied heart of the dog.

Myocardial transcapillary exchange was investigated in control hearts and in two types of hypertrophied hearts: exercise hypertrophy and pathological hypertrophy due to tricuspid insufficiency. Using the single-injection indicator diffusion method (6, 28), myocardial extractions (E), capillary clearances (C), and permeability surface area products (PS) of urea, sucrose, and inulin were measured in intact, pump-perfused, working hearts of anesthetized dogs. Both types of cardiac hypertrophy were associated with a decreased coronary vascular resistance. Myocardial E, C, and PS values from the exercised group were not significantly different from control. Dogs with pathological hypertrophy exhibited increased central venous pressures, RVEDP's, and heart rates which were greater than control values. The E, C, and PS values from the pathologically hypertrophied hearts were significantly greater than control. These increases in myocardial transcapillary exchange can be explained either by increasing the equivalent pore radius of myocardial capillary membranes from a control value of 70 to 100 A or by assuming that pathologically hypertrophied hearts have a myocardial capillary surface area available for exchange which is twice that of control hearts.

Animals↗

Parameter identification in coronary pressure flow models: a graphical approach.

The confident identification of parameters is important in the practical application of physiological models. However, the task of parameter identification is often complicated by interactions among parameters and by the fact that the sensitivity of the model to changes in a given parameter is generally a function of all the other parameters. Here we illustrate a graphical approach to parameter identification that allows the modeler to visualize the behavior of the model, the sensitivity functions, and certain functions characteristic of parameter interdependence. The visual display can be generated over any desired portion of parameter space. The technique is applied to a simple, four-parameter, myocardial pump model of the coronary circulation. The results indicate that over specified ranges of parameters, it is possible to distinguish among the four parameters of the model: the ratio of proximal-to-distal resistance, alpha; the overall resistance of the vascular bed, R; the compliance of the vascular bed, C; and a parameter, kappa, relating tissue pressure to left ventricular pressure. It was found that in order to identify all parameters uniquely, it was necessary to regress upon both coronary inflow and outflow.

Blood Pressure↗

Restenosis following placement of an intracoronary heparin treated tantulum stent in the hyperlipidemic miniature swine model.

Restenosis persists as an important factor limiting a favorable long term outcome following mechanical revascularization. The objective of the present study was to compare the effects of an intracoronary heparin treated tantalum prototype stent and balloon angioplasty on intimal hyperplasia, luminal diameter, and thrombosis in a porcine restenosis model. Male miniswine maintained on a high cholesterol diet and 325 mg aspirin per day underwent cardiac catheterization and oversized balloon injury to the right and left circumflex coronary arteries. Two weeks later one artery was either balloon injured again or implanted with a stent. No additional anticoagulation following stent placement was given, however aspirin was continued throughout the study. At four weeks, the coronary arteries were harvested and prepared for histologic examination and blinded quantitative morphometric analysis. The prototype stent was successfully deployed in 10 coronary arteries. Histological examination at explant revealed no evidence for thrombus or platelet aggregation. The angiographic luminal diameter of stented vessels was not significantly different from the diameter measured prior to implantation. In contrast, the angiographic diameter of balloon injured vessels was significantly decreased (4.4 +/- 0.4 mm2, balloon injured, vs. 5.8 +/- 3.3 mm2, control; p < 0.05). Stented arteries showed significantly more intimal hyperplasia, compared to balloon injured vessels (2.99 +/- 0.58 mm2 intimal area, stented arteries vs. 0.38 +/- 0.15 mm2 intimal area, control arteries; p < 0.05). In conclusion, heparin treated tantalum wire prototype intracoronary stents were successfully deployed in swine coronary arteries with no evidence for thrombus formation. Despite a significant intimal response, luminal diameter was preserved in stented vessels. The data suggest that a heparin treated tantalum wire prototype intracoronary stent may be an effective method of coronary revascularization that results in the preservation of luminal diameter without thrombotic occlusion.

Angioplasty, Balloon, Coronary↗