Search PubMed⌕ Search

Biomedical subjects

A S Most

Publications and source records attributed to A S Most.

At least 37 records · Page 2Linked to original sources
PubMed1987

Measurement of plasma adenosine concentration: methodological and physiological considerations.

This study tested the hypothesis that measurements of plasma adenosine concentration made on samples of blood obtained in dipyridamole and EHNA (i.e., "stopping solution") may be falsely elevated as a result of ongoing in vitro production and accumulation of adenosine during sample processing. Studies were performed with samples of anticoagulated blood obtained from anesthesized domestic swine. Adenosine concentration of ultra filtrated plasma was determined by high-pressure liquid chromatography (HPLC). The following parameters were evaluated: (i) rate of clearance of [3H]adenosine added to plasma, (ii) endogenous adenosine concentration of matched blood samples obtained in "stopping solution" alone, "stopping solution" plus EDTA, and perchloric acid (PCA), (iii) plasma and erythrocyte endogenous adenosine concentration in nonhemolyzed samples, and (iv) plasma adenosine concentration of samples hemolyzed in the presence of "stopping solution" alone or "stopping solution" plus EDTA. We observed that (i) greater than or equal to 95% of [3H]adenosine added to plasma is removed from it by formed elements of the blood in less than 20 s, (ii) plasma adenosine concentration of samples obtained in "stopping solution" alone is generally 10-fold greater than that of matched samples obtained in "stopping solution" plus EDTA, (iii) deliberate mechanical hemolysis of blood samples obtained in "stopping solution" alone resulted in substantial augmentation of plasma adenosine levels in comparison with matched nonhemolyzed specimens--addition of EDTA to "stopping solution" prevented this, and (iv) adenosine content of blood samples obtained in PCA agreed closely with the sum of plasma and erythrocyte adenosine content of samples obtained in "stopping solution" plus EDTA. The data obtained demonstrate that (i) plasma adenosine concentrations are falsely elevated in samples of blood obtained in "stopping solution" alone, and (ii) addition of EDTA to "stopping solution" blocks in vitro production and accumulation of adenosine. Finally, rapid removal of adenosine from plasma by formed elements of blood may make it difficult to employ measurements of plasma adenosine concentration to assess physiological processes even in the absence of in vitro production of the nucleoside.

Adenine↗
PubMed1986

Sustained efficacy of percutaneous transluminal coronary angioplasty.

To determine whether the immediate efficacy of percutaneous transluminal coronary angioplasty (PTCA) is sustained, follow-up data were obtained in 183 patients who had undergone PTCA at least 1 year earlier. The duration of follow-up ranged from 1 to 5 years. Subjective clinical information was obtained in each patient and objective functional information, determined by exercise stress testing, was obtained in 91. PTCA was initially successful in 141 patients (79%). Of the 42 patients in whom PTCA was unsuccessful, 26 underwent coronary artery bypass graft surgery (CABG), while 16 were maintained on medical therapy (MED). When compared to the MED patients at time of follow-up, successful PTCA patients experienced less angina (13% vs 47%; p = 0.003), used less nitroglycerin (25% vs 73%, p = 0.003), were hospitalized less often for chest pain (8% vs 31%; p = 0.02), and subjectively felt their condition had improved (96% vs 20%; p less than 0.001). Furthermore, during exercise testing, the prevalence of angina was reduced (9% vs 43%; p = 0.05), and exercise duration was greater (8.2 minutes vs 5.8 minutes, p = 0.05) among PTCA patients. There were no significant differences in the incidence of subsequent myocardial infarction, mortality, or need for coronary artery bypass surgery. For these variables, no differences were seen between the CABG and PTCA groups. Thus, successful PTCA results in long-term relief of subjective and objective manifestations of myocardial ischemia, superior to that of medical therapy and comparable to CABG.

Angina Pectoris↗
PubMed1986

Role of adenosine in mediating myocardial blood flow response to isoproterenol: observations in closed chest, sedated, domestic swine.

To test the hypothesis that adenosine is required to mediate the sustained increase in myocardial flow evoked by isoproterenol haemodynamic indices, myocardial blood flow (microspheres), and regional myocardial oxygen consumption were measured in eight closed chest, sedated pigs at control, after isoproterenol (6.9(2.8) ng X kg-1 X min-1 (mean (SD)) infused into the left anterior descending coronary artery, repeat control, and after a simultaneous infusion of the same dose of isoproterenol and adenosine deaminase (10 U X kg-1 X min-1). Data were acquired at one and 10 minutes after each infusion and compared with control measurements. Heart rate was held constant by atrial pacing. Peak left ventricular dP/dt (mm Hg X s-1) increased significantly (control 2190(32) mean (SD)) at both one (2900(302)) and 10 minutes (3010(391)) of isoproterenol infusion alone. At one minute of simultaneous infusion there was no change (control 1970(447)) in left ventricular dP/dt (2290(521)), although dP/dt was significantly increased at 10 minutes of simultaneous infusion (2790(483)). Transmural flow (ml X min-1 X g-1) increased significantly (control 1.49(0.46)) in the distal left anterior descending zone at one (1.94(0.48)) and 10 minutes (2.07(0.27)) of isoproterenol infusion alone. In contrast, flow failed to increase (control 1.65(0.27)) during the first minute of simultaneous infusion (1.73(0.38)), although it did increase significantly by 10 minutes (1.91(0.21). Finally, although myocardial oxygen consumption (ml X min-1 X 100 g-1) increased significantly (control 16.4(4.7)) at both one (20.1(4.7)) and 10 minutes (19.4(3.6)) of isoproterenol infusion alone, it failed to increase (control 18.2(3.8)) at one (19.3(4.6)) and 10 minutes (19.1(3.8)) of simultaneous infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Adenosine's role in regulating basal coronary arteriolar tone.

This study examined the role of adenosine in regulating coronary arteriolar tone under basal conditions in the normal coronary circulation. Measurements of hemodynamics and flow (microspheres) were made in eight closed-chest, sedated pigs at 1) control and 2) after 10 min of infusion of adenosine deaminase (ADA, 10 U X kg-1 X min-1) into the left anterior descending (LAD) coronary artery. Heart rate was held constant by atrial pacing. Transmural flow in the distal LAD zone did not change versus control (1.81 +/- 0.36) with ADA (1.78 +/- 0.46). However, in comparison with control the distal LAD:circumflex zone transmural flow ratio (0.96 +/- 0.04) declined (P less than 0.01) during ADA infusion (0.93 +/- 0.04). Similarly, the distal LAD:circumflex zone transmural flow resistance ratio increased significantly (P less than 0.01) versus control (1.04 +/- 0.05) in response to intracoronary ADA infusion (1.08 +/- 0.04). Regional myocardial oxygen consumption in the distal LAD zone did not change versus control (16.9 +/- 3.3 3.3 ml X min-1 X 100 g-1) during ADA (16.9 +/- 4.5). Additional studies in 15 open-chest swine given intracoronary infusion of ADA demonstrated that 1) the enzyme penetrates the interstitial fluid (ISF) and 2) attains ISF levels which are adequate to reduce basal adenosine concentration 10 fold even if substantial increase in adenosine production occurs in response to ADA. Thus, since destruction of adenosine by ADA caused only very modest relative reduction in regional flow, it is likely that the nucleoside plays only a limited role in regulation of arteriolar tone under basal conditions in the normal coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Prediction of long-term clinical outcome with final translesional pressure gradient during coronary angioplasty.

The final translesional pressure gradient measured during coronary angioplasty correlates with immediate angiographic and clinical results. Whether the pressure gradient is of value in predicting late clinical outcome has not been determined. We therefore obtained complete follow-up information on 159 patients with single-vessel disease who underwent successful coronary angioplasty. Mean follow-up time was 15 +/- 10 months. The occurrence of repeat angioplasty, coronary bypass surgery, recurrent anginal chest pain, or a positive postangioplasty stress test were considered clinical events indicative of late failure. Of the variables age, gender, initial and final translesional pressure gradient, extent of initial and final arterial narrowing, site of dilatation, type of balloon catheter used, number of inflations, and maximal inflation pressure, only the final translesional pressure gradient was predictive of late failure when analyzed by multivariate techniques. Thus, the final translesional pressure gradient is of value in predicting both immediate and late outcome after coronary angioplasty.

Aged↗
PubMed1986

Effect of a reduction in blood viscosity on maximal myocardial oxygen delivery distal to a moderate coronary stenosis.

This study tested the hypothesis that a reduction in blood viscosity by means of isovolumetric hemodilution will permit an increase in maximal oxygen delivery to myocardium distal to a moderate coronary arterial stenosis. It is known that blood viscosity is a determinant of resistance to blood flow at both the stenotic and the arteriolar levels. Accordingly, a reduction in blood viscosity could exert a favorable influence on maximal myocardial oxygen delivery in the setting of stenosis, provided that the oxygen-carrying capacity of the blood is not compromised excessively. Closed-chest, sedated domestic swine (n = 8) were instrumented with an artificial coronary arterial stenosis that reduced vessel diameter by 64%. Measurements of hemodynamics, regional myocardial blood flow (microspheres), lactate and oxygen metabolism, and whole blood viscosity were made at control and after two successive 10 min intracoronary infusions of adenosine (400 and 800 micrograms/min) distal to the stenosis. Next, albumin/saline solution was given intravenously to reduce the animal's hematocrit by approximately 50%. Repeat measurements of all experimental variables were then made at a second control and again after two successive 10 min intracoronary infusions of adenosine (400 and 800 micrograms/min) distal to the stenosis. Myocardial blood flow (ml/min/g) distal to the stenosis increased from 1.52 +/- 0.21 (mean +/- 1 SD) to 4.10 +/- 0.86 in response to adenosine (peak dose) before hemodilution (p less than .01) and from 2.07 +/- 0.59 to 4.08 +/- 0.93 (p less than .01) after hemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1985

Elevated coronary vascular resistance in the presence of reduced resting blood flow distal to a severe coronary stenosis.

Vascular reserve in underperfused myocardium has recently been described. This seemingly paradoxical observation conflicts with older concepts of the coronary circulation which hold that flow deficits do not develop until reserve is fully exhausted. To examine this phenomenon in greater detail in an animal model mimicking a fixed human coronary artery stenosis, we analysed the records of 25 carefully selected, sedated pigs all instrumented with a rigid intralumenal coronary stenosis (82% lumenal diameter reduction). Each animal satisfied the following criteria: 1) perfused myocardial mass beyond the stenosis was within a narrow weight range (16 to 24 g); and 2) post stenosis (distal) epicardial (Epi) and endocardial (endo) flows were less than or equal to 90% of respective flows in a region perfused by the non-stenosed circumflex (CX) coronary artery. Accordingly, distal flow was reduced compared to circumflex zone flow (p less than 0.01) in the Epi (173 +/- 51 to 113 +/- 32 ml . 100g-1 . min-1), Endo (146 +/- 39 to 116 +/- 27) and transmural (Tm) regions (164 +/- 45 to 124 +/- 31). Despite a flow deficit and constant severity of stenosis, distal zone Tm resistance (0.55 +/- 0.21 mmHg/ml . 100 g-1 . min-1) exceeded the minimum level achievable with intravenous infusion of adenosine (0.25 +/- 0.07) in a separate group of eight animals without a stenosis. Distal transmural resistance also varied over a five fold range (0.27 to 1.33) and in 20/25 animals exceeded the highest level (0.37) seen in non-stenosis animals during adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1985

Impaired arteriolar vasodilation induced by thrombosis of a coronary arterial stenosis.

This study tested the hypothesis that aggregation of platelets and release of thromboxane A2 at the site of a coronary arterial stenosis may contribute to myocardial ischemia by impairing flow regulation of the distal coronary bed. Measurements of hemodynamics, flow (microspheres), lactate metabolism, and prostaglandin (PG) metabolites (thromboxane B2 and 6-keto-PGF1 alpha) were made in closed-chest anesthetized pigs instrumented with a stenosis (65% diam reduction) in the left anterior descending (LAD) coronary artery. Data were acquired prior to stenosis insertion (control) and 5 and 15 min after insertion, during which time thrombotic occlusion of the device was occurring. Heart rate was controlled by atrial pacing. Distal LAD zone endocardial flow (ml X min-1 X g-1) declined versus control (1.15 +/- 0.20, mean +/- SD) at 5 min (0.89 +/- 0.40, P less than 0.05) and 15 min (0.41 +/- 0.36, P less than 0.01) of occlusion. Distal endocardial resistance (mmHg X ml-1 X min X g), however, did not change versus control (72 +/- 12) at 5 (66 +/- 12) or 15 min (61 +/- 38). Distal epicardial resistance (mmHg X ml-1 X min X g) declined versus control (90 +/- 17) at 5 (66 +/- 35, P less than 0.05) and 15 min (43 +/- 26, P less than 0.01) postinsertion. Finally, lactate extraction (%) at control (42 +/- 19) changed to production 15 min postinsertion (-36 +/- 93, P less than 0.05) and arterial-anterior interventricular vein thromboxane B2 difference (pg/0.1 ml) changed from 13.1 +/- 17.8 pre to -15.8 +/- 30.0 at 5 min post (P less than 0.05). Thus platelet aggregation and release at a spontaneously thrombosing stenosis contribute to ischemia not only by reduction of stenosis diameter but also by impairment of flow regulation in endocardial layers distal to it.

Animals↗
PubMed1985

Adaptation to the stress of tachycardia in patients with coronary artery disease: insight into the mechanism of the warm-up phenomenon.

Adaptation to exercise or the "warm up phenomenon" has been observed in some patients with angina pectoris. To investigate adaptation, eleven patients with exertional angina pectoris and angiographic evidence of coronary artery disease underwent two identical bouts of sequential tachycardia stress separated by a brief recovery period. Manifestations of ischemia were less during the second stress, as evidenced by a reduction in the severity of angina pectoris, less ST segment depression, and improved lactate extraction. Peak coronary blood flow during the second stress (81 +/- 20 ml/min) was not significantly different from that during the first (95 +/- 32 ml/min). Regional myocardial oxygen consumption, however, was significantly (p = .03) lower during the second stress (8.8 +/- 2.4 ml O2/min) when compared with the first (11.4 +/- 3.0 ml O2/min). Thus, patients with coronary artery disease can develop anginal tolerance to the stress of tachycardia similar to that observed after repeated bouts of exercise. A relative reduction in myocardial oxygen consumption, rather than an increase in coronary blood flow, appears to account for this phenomenon.

Adaptation, Physiological↗
PubMed1985

Measurement by electrical impedance aggregometry of porcine platelets response to selected physiological agonists.

Although the domestic swine is commonly employed for physiological studies of the coronary circulation, there is relatively little data available concerning the responsiveness in whole blood of normal porcine platelets to standard physiological agonists. Such information is essential if the domestic swine is to be used as an animal model for studying potential interactions between platelets and the coronary circulation. Accordingly, the present study was undertaken to characterize the responses (aggregation and ATP release) observed in whole blood of normal porcine platelets to selected physiological agonists. The responses of platelets from 10 normal human volunteers also were studied with this system for comparison. Agents tested included ADP, arachidonic acid, collagen, epinephrine, norepinephrine, and thrombin. Studies were conducted with the Chronolog impedance aggregometer. The results demonstrate that platelets of domestic swine are reactive to ADP, arachidonic acid, and collagen. In contrast, neither epinephrine nor norepinephrine alone induced aggregation or release. Norepinephrine, however, caused modest potentiation of aggregation in response to ADP only. At 1 mM concentration each catecholamine inhibited the release response to collagen while at 10 mM each inhibited aggregation and release in response to either ADP or collagen. The data obtained indicate the domestic swine may be employed as a useful model to examine interactions between platelets and the coronary circulation.

Adenosine Diphosphate↗
PubMed1984

Limitations of visual assessment of redistribution in thallium images.

Potential limitations of visual assessment of redistribution in thallium (TI) images were studied and results were compared with computer assessment of redistribution. A four-section phantom filled with TI was imaged (300K counts, 128 X 128 matrix) with appropriate background activity and scatter material. Activity in a "defect" section (DS) was varied from 20% to 100% of reference sections (RS). After interpolative background correction, pseudo "initial" and "late" image pairs (N = 35) were photographed on polaroid film and read by three "blinded" observers using an 0-2, 1/2 step, scale (0 = absent and 2 = normal activity). Scan defects were detected by all readers when DS activity was less than or equal to 59% of RS activity. No reader detected a defect when DS activity was greater than or equal to 67% of RS activity. All "initial" defects were detected by computer analysis. Visual assessment of "initial" DS:RS activity ratio did not correlate well with DS:RS activity ratio of the phantom. In contrast, computer assessment of "initial" DS:RS activity ratio correlated well with phantom DS:RS activity ratio (r = 0.96, p less than .0001). Although 22 of 27 scan pairs with partial (N = 26) or full (N = 1) redistribution were correctly identified as showing redistribution by at least two of three observers, the extent of redistribution was not estimated well by visual analysis. Thus, visual assessment of absolute change ("initial"-to-"late") in DS:RS activity ratio showed considerable scatter in relations to actual changes in DS:RS activity ratio of the phantom.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗
PubMed1984

Recovery of myocardial function following brief versus prolonged atrial pacing stress in the presence of coronary artery stenosis.

The ability of myocardium distal to a severe coronary artery stenosis to recover from brief (5 min) versus prolonged (30 min) atrial pacing stress was compared in this study. Eight closed chest pigs were prepared with a coronary artery stenosis (82% lumenal diameter reduction) in the left anterior descending artery and ultrasonic length sensors in left anterior descending endocardium. Extent of recovery of systolic function 5 min following a brief (5 min) period of ischaemia induced by rapid (175 to 190 min-1) atrial pacing (AP-1) was compared with that following a prolonged (30 min) period of ischaemia induced by rapid atrial pacing (AP-2). Regional myocardial blood flow (ml X min-1 X g-1) was measured at control, during, and following atrial pacing. Regional shortening (%) distal to the stenosis declined versus control at both 5 min of AP-1 (10.0 +/- 7.3 (mean +/- 1 SD) to 0.6 +/- 0.9, p less than 0.01) and 30 min of AP-2 (6.8 +/- 3.3 to 2.1, +/- 3.5, p less than 0.01). However, within 5 min of discontinuing both brief as well as prolonged pacing, regional segmental shortening (5.7 +/- 3.9 and 7.0 +/- 6.9, respectively) returned to 50 to 70% of initial control levels (10.0 +/- 7.3). Regional shortening was similar 5 min following brief and prolonged stress. Distal left anterior descending zone epicardial regional myocardial blood flow increased (p less than 0.01) versus control at AP-1 (1.05 +/- 0.24 to 1.39 +/- 0.24) and 30 min of AP-2 (0.99 +/- 0.21 to 1.40 +/- 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Influence of adenosine on basal myocardial function: observations in anaesthetised, domestic swine.

Data from experiments in isolated cardiac muscle preparations indicate that adenosine in high concentration (10(-3) mol X litre-1) exerts a negative inotropic effect on the myocardium under basal conditions. The following study was performed to test the hypothesis that adenosine exerts a similar negative inotropic effect when administered in an intact animal model in a dose sufficient to cause maximal coronary vasodilatation. Six open chest anaesthetised pigs were studied as follows. Ultrasonic length sensors were placed in the endocardium of the free wall of the left ventricle in a region perfused by the left anterior descending (LAD) coronary artery. Large increases in endocardial blood flow in response to adenosine administration, which could enhance segmental function ("garden hose effect"), were prevented by inserting an artificial stenosis (73% reduction in lumenal diameter) in the proximal third of the LAD. Measurements of haemodynamics, regional myocardial blood flow (microsphere technique), and regional systolic function were made at control 1, at the end of 10 min of intracoronary adenosine infusion (3.0 mumol X min-1) at a dose which exceeded that previously shown to cause maximal coronary vasodilatation and at second control 20 to 40 min after discontinuation of adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1984

Lateral position improves wedge-left atrial pressure correlation during positive-pressure ventilation.

Because lateral position can be used to locate a pulmonary artery catheter tip in lung regions where venous pressure exceeds alveolar pressure, we studied the effect of lateral position on the correlation between pulmonary artery occlusion pressure (Pw) and left atrial pressure (Pla) at various increments of positive-end expiratory pressure (PEEP). In ten normal anesthetized pigs, catheters were placed in the left atrium and right and left pulmonary arteries; simultaneous measurements of Pla and Pw from both catheters were obtained in the supine, right lateral, and left lateral positions. Pw obtained in the lateral position when the catheter tip was vertically located below the left atrium ("lower") more accurately reflected Pla changes than Pw obtained from catheters above the left atrium, at PEEP levels less than 20 cm H2O. Although most catheter tips were located below the left atrium in the supine position, our data from the lower catheter more accurately assessed Pla than did the Pw obtained in the supine position; this was particularly evident when the catheter tip was located vertically above the left atrium. These findings suggest that the lateral position can be useful in measuring Pw during continuous positive-pressure ventilation. However, further studies in humans are needed before this maneuver can be recommended.

Animals↗
PubMed1984

Contrasting effects of nifedipine and adenosine on regional myocardial flow distribution and metabolism distal to a severe coronary arterial stenosis: observations in sedated, closed-chest, domestic swine.

This study tested the hypothesis that intrinsic negative inotropic effects of a drug used to induce coronary vasodilation distal to a severe coronary arterial stenosis may influence the extent of redistribution of transmural flow and its metabolic consequences. To test this hypothesis, studies were conducted in eight closed-chest, sedated swine with severe (82% reduction in luminal diameter) coronary arterial stenoses. Measurement of hemodynamic parameters, regional myocardial blood flow (microsphere technique), lactate metabolism, and oxygen consumption were made (1) under control conditions, (2) after 10 min of intracoronary infusion of a vasodilator distal to the stenosis, and (3) under repeat control conditions. Each animal received both intracoronary adenosine (400 micrograms/min) and nifedipine (50 micrograms/min). The order of drug infusion was chosen at random and a control period separated administration of each. In response to nifedipine there was no significant change in the group mean (+/- SD) value of endocardial flow (1.21 +/- 0.34 to 1.29 +/- 0.61 ml/min X g-1) distal to the stenosis. In contrast, epicardial flow increased in comparison with control in response to nifedipine (1.30 +/- 0.58 to 1.79 +/- 0.74 ml/min X g-1; p less than .05). Regional myocardial oxygen consumption (MVO2) declined in comparison with control in response to nifedipine (14.0 +/- 4.2 to 11.1 +/- 5.0 ml/min X 100 g-1; p less than .05). Regional lactate extraction did not change in comparison with control during infusion of nifedipine (18.2 +/- 22.4 vs 11.7 +/- 16.8). In response to adenosine, endocardial blood flow distal to the stenosis declined in comparison with control (1.25 +/- 0.53 to 1.07 +/- 0.38 ml/min X g-1; p less than .05), while epicardial flow increased (1.31 +/- 0.55 to 2.26 +/- 0.59 ml/min X g-1; p less than .01). Regional MVO2 also tended to decline in comparison with control in response to adenosine (13.4 +/- 4.9 to 11.7 +/- 2.9 ml/min X 100 g-1) and was significantly (p less than .05) reduced in comparison with postintervention control (14.6 +/- 4.2 ml/min X 100 g-1). In contrast to nifedipine, adenosine caused a significant decline in regional lactate extraction in comparison with control (12.7 +/- 23.2% to -40.6 +/- 55.0%; p less than .01). Thus, administration of nifedipine, a negative inotropic agent, resulted in (1) a decline in regional MVO2, (2) increased epicardial blood flow with variable effects on endocardial flow distal to the stenosis, and (3) no evidence of de novo or worsening ischemia, even in animals in which endocardial flow decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗