Myocardial turnover of plasma free fatty acids during angina pectoris induced by atrial pacing

Myocardial extraction of free fatty acids (FFA), together with glucose, lactate, pyruvate, glycerol and oxygen was determined by simultaneous sampling of blood from an artery (a) and the coronary sinus (cs) at rest and during chest pains induced by atrial pacing in seven fasting male patients with ischaemic heart disease. Results were compared to those, at rest and during pacing at heart rate 140 beats min^-1 in ten healthy men of similar age. A continuous i.v. infusion of ¹⁴C oleate and ³H palmitate enabled the calculation of simultaneous myocardial uptake and release of FFA. as well as of the fraction of extracted FFA which underwent direct oxidation. During chest pain lactate net extraction decreased to become, in some patients, negative. FFA extraction, as estimated from the fractional extraction of labelled fatty acid was likewise decreased, while the a-cs O₂ difference was not significantly altered. The fractional oxidation of extracted FFA was increased, whereas the calculated fatty acid release from the heart was unaltered. The increase in fractional oxidation was quantitatively correlated with the decrease in lactate extraction suggesting that it was related to the degree or extent of ischaemia. It was also proportional to the decrease in FFA extraction. Thus, in patients with angina pectoris the ischaemic myocardium may be subjected to a limitation not only with regard to oxygen but also substrate flux into the myocardial cells.     

Effect of experimental non-insulin requiring diabetes on myocardial microcirculation during ischaemia in dogs

Abstract To examine whether chronic high blood glucose may influence myocardial microcirculation during acute myocardial ischaemia in the dog, a non-insulin-requiring diabetes was induced by the streptozotocin-alloxan method. Seventy-five days later, myocardial ischaemia was provoked by occluding the left anterior descending coronary artery for 2h and micro-circulation regulation was assessed in the ischaemic and non-ischaemic myocardium by the radioactive microsphere method. Diabetic dogs were compared with normal dogs. Diabetic dogs had higher blood glycated haemoglobin (2·66±0·4%) and fructosamine (397±62 μ mol l^-1) than control dogs (0·66±0·2, P <0·004 and 229 ± 13, P <0·03, respectively). Haemodynamic data in the two groups were not different at any time. The size of the ischaemic zone was similar in both groups. During the 2h ischaemia in the ischaemic zone subendocardial ( P = 0·22) and subepicardial ( P <0·05) blood flow slightly increased in control dogs whereas there was a 63% ( P <0·02) and 35% ( P = 0·06) reduction respectively in diabetic dogs. In the non-ischaemic zone, blood flow of controls tended to increase ( P <0·006 in the subepicardium and P <0·06 in the subendocardium) whereas in diabetic dogs blood flow tended to decrease ( P = 0·03 in the subendocardium and in the subepicardium). This first investigation on myocardial microcirculation in diabetic dogs during ischaemia suggests that one of the possible causes of increased mortality rate from ischaemic cardiac disease in diabetics might be related to a paradoxical and unfavourable pattern of myocardial blood flow during ischaemia.     

内毒素血症对左室心肌血液灌流和血液分配的影响

目的：观察内毒素血症对左室心肌血液灌流和血液分布的影响。方法：２８只家兔随机分成４组,每组７只（对照组、内毒素组、抗体保护组和无关抗体组）。后３组静注内毒素（０．１ｍｇ／ｋｇ）,对照组注射等量生理盐水。内毒素注射前３０分钟抗体保护组和无关抗体组各静注相应抗肿瘤坏死因子（ＴＮＦ）单克隆抗体（５ｍｌ／ｋｇ）和抗白介素－２（ＩＬ－２）单克隆抗体（５ｍｌ／ｋｇ）。使用放射性生物微球技术测量左室心肌血液灌流     

Haemodynamic and metabolic effects of combined adrenergic α- and β-receptor blockade with labetalol in the exercising human forearm

At rest supine acute intravenous administration of the combined adrenergic alpha- and beta-receptor blocking compound labetalol (1 mg/kg body weight) to young, healthy, male subjects, produced a clear-cut fall in arterial blood pressure. During dynamic forearm exercise, forearm blood flow decreased by 17.2%, and calculated vascular resistance increased by 11.3% after labetalol. Forearm oxygen uptake decreased (14.6%), suggesting an increased mechanical efficiency. Lactate release from the exercising forearm decreased (17.6%), probably because of the beta-receptor blockade. Forearm uptake of glucose and free fatty acids remained unchanged. Arterial blood glucose concentration attained a higher level after labetalol. Arterial plasma concentration of FFA was reduced during exercise and post-exercise probably because beta-receptor mediated lipolysis was antagonized.     

Hepatic metabolism of free fatty acids in normal and diabetic dogs

Fasted dogs prepared with catheters in the femoral artery, portal vein, and hepatic vein and infused intravenously with palmitate-1-(14)C were used to estimate uptake of free fatty acids in liver and their conversion to major metabolic products secreted into hepatic venous blood. Animals were studied under ordinary conditions and when fat mobilization was increased abruptly by infusing norepinephrine or for a prolonged period by withdrawing insulin from depancreatized dogs. 80% of hepatic blood flow was assumed to be derived from the portal vein.Hepatic uptake was proportional to net outflow transport of plasma free fatty acids in the three groups and, in each, hepatic extraction fraction was about 25%. Since specific activity of free fatty acids entering and leaving the liver was equal and their composition was closely similar in the three sites sampled, it was concluded that palmitate is a representative tracer for free fatty acids entering the liver and that the liver does not release free fatty acids into the blood.In norepinephrine-infused dogs, the fraction of free fatty acids secreted in triglycerides (13%) was similar to that of control animals, so that transport of triglycerides was increased. In diabetic dogs no increased transport could be demonstrated since an average of only 2% of free fatty acids was converted to plasma triglyceride fatty acids; the hyperlipemia uniformly observed therefore appeared to result from defective removal of triglycerides from the blood.A similar fraction of free fatty acids was converted to ketones in normal and norepinephrine-infused dogs. This fraction was somewhat higher in diabetic animals and, in addition, a substantial quantity of ketones was derived from unlabeled precursors. Fractional conversion of free fatty acids to CO(2) was similar in normal and norepinephrine-infused dogs, but reduced in the diabetics.     

A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility

The purpose of the present study was to clarify how endogenous nitric oxide (NO) affects cardiac contractility and myocardial oxygen consumption (MVO2) in vivo. alpha-Chloralose-anesthetized dogs (n = 18) were instrumented to perform continuous and simultaneous measurements of coronary blood flow (CBF), anterior interventricular vein oxygen saturation (with the use of a fiberoptic catheter), aortic pressure, left ventricular pressure, and left ventricular volume. CBF, myocardial oxygen extraction (O2-extract), MVO2, the relationship between CBF and O2-extract during direct vasodilation induced by intracoronary papaverine (0.1, 0.2, 0.4 mg/kg), and cardiac contractility (Emax) were examined at control, after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA, 2 mg/kg) and after antagonization of NO by L-arginine (20 mg/kg). L-NMMA decreased CBF from 62.0 +/- 1.7 to 59.7 +/- 2.4 (mL/min/100 g, P < 0.05) and increased O2-extract from 68.2 +/- 1.7 to 79.0 +/- 1.7% (P < 0.05). Emax was increased after L-NMMA from 3.2 +/- 0.2 to 3.7 +/- 0.1 (mmHg/mL/100 g, P < 0.05). These effects of L-NMMA were antagonized by L-arginine (P < 0.05 vs. after L-NMMA, P = NS vs. before L-NMMA). L-NMMA shifted CBF and O2-extract relationship determined by papaverine injection upward and L-arginine antagonized it to its baseline level. Endogenous NO reduces cardiac contractility and decreases MVO2, while increasing CBF.     

Regional blood flow during cardiopulmonary resuscitation with abdominal counterpulsation in dogs

The addition of abdominal counterpulsation to standard cardiopulmonary resuscitation (AC-CPR) during ventricular fibrillation has been shown to improve cardiac output, oxygen uptake, and central arterial blood pressure in dogs. The present study was performed to determine the effect of AC-CPR on regional blood flow. Regional blood flow was measured with radioactively labeled microspheres during sinus rhythm and during alternate periods of AC-CPR and standard CPR (STD-CPR) in nine dogs anesthetized with pentobarbital. Blood pressures and oxygen uptake were measured continuously. As in previous studies, diastolic arterial pressure was higher (30.8%) during AC-CPR than during STD-CPR, as were cardiac output (24.5%) and oxygen uptake (37.5%). Whole brain and myocardial blood flow increased 12.0% and 22.7%, respectively, during AC-CPR. Blood flow to abdominal organs was not changed appreciably in response to abdominal compression, and postmortem examination revealed no gross trauma to the abdominal viscera. The AC-CPR technique is simple and is easily added to present basic life support procedures. In light of the improvements observed in myocardial and cerebral blood flow, AC-CPR could significantly improve the outcome of CPR attempts.     

The effects of oral sucrose and of estimated infarct size on plasma free fatty acids, plasma glucose and serum insulin in the early stages of acute myocardial infarction

Abstract. Twenty-two patients with early myocardial infarction were studied to test the effect of oral sucrose as an antilypolytic agent. Without sucrose, plasma free fatty acids rose to a peak (mean 1.48 mM/l 8 h after onset of symptoms) and then fell spontaneously by 32% of the peak level in 2 h. Sucrose had no effect on the peak fatty acid level and did not accelerate the initial rate of fall in the first 2 h. Where the peak free fatty acid was less than 1.5 mM/l, however, it fell to a lower level in patients given sucrose ( P < 0.05). A subsequent rebound of free fatty acid values, as seen in starved patients, was delayed for about 6 h in sucrose-fed patients. The responses of free fatty acid, glucose and insulin varied according to the size of the infarct as estimated by the plasma creatine kinase method. Patients with larger infarcts (>65 creatine kinase gram equivalents) had higher insulin and blood sugar levels on and after admission, and had higher plasma free fatty acid peaks than patients with smaller infarcts (≤65 creatine kinase gram equivalents). When patients with larger infarcts were given oral sucrose, the rise in blood glucose was higher and more sustained than in patients with small infarcts and there was no insulin response. The insulin response to sucrose was normal in those with smaller infarcts. Thus oral sucrose was an effective antilipolytic agent only in patients with smaller infarcts.     

Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man.

Plasma FFA oxidation (measured by infusion of 14C-palmitate) and net lipid oxidation (indirect calorimetry) are both inhibited by insulin. The present study was designed to examine whether these insulin-mediated effects on lipid metabolism resulted from a decline in circulating FFA levels or from a direct action of the hormone on FFA/lipid oxidation. Nine subjects participated in two euglycemic insulin clamps, performed with and without heparin. During each insulin clamp study insulin was infused at two rates, 4 and 20 mU/m2.min for 120 min. The studies were performed with indirect calorimetry and 3-3H-glucose and 14C-palmitate infusion. During the control study plasma FFA fell from 610 +/- 46 to 232 +/- 42 to 154 +/- 27 mumol/liter, respectively. When heparin was infused basal plasma FFA concentration remained constant. During the control study, FFA/lipid oxidation rates decreased in parallel with the fall in the plasma FFA concentration. During the insulin/heparin study, plasma 14C-FFA oxidation remained unchanged while net lipid oxidation decreased. In conclusion, when the plasma FFA concentration is maintained unchanged by heparin infusion, insulin has no direct effect on FFA turnover and disposal. These results thus suggest that plasma FFA oxidation is primarily determined by the plasma FFA concentration, while net lipid oxidation is regulated by both the plasma FFA and the insulin level.     

Effect of coronary bypass surgery on anaerobic myocardial lactate metabolism during pacing-induced angina pectoris

Myocardial lactate metabolism was studied by coronary sinus catheterization in nine patients before and 8–12 months after coronary bypasss surgery. Measurements were performed at rest and during atrial pacing increased to a heart rate which produced strong chest pain. The estimation of myocardial lactate extraction and release was facilitated by a constant rate infusion of ¹⁴C lactate and coronary sinus blood flow (CSBF) was measured by thermodilution. Pre-operatively strong chest pain could be elicited in all patients and isotope data indicated a significant myocardial lactate release in all of them, although the net a-cs difference was negative in only half of them. After bypass surgery the maximum tolerable heart rate was increased by 23 beats min¹ and chest pain both at heart rate 110 beats min¹ and at the highest heart rate achieved was reduced or absent in eight of the nine patients. The increase in chest pain during pacing was quantitatively related to the increase in myocardial lactate release, and the correlation between these two variables followed the same course after the operation as it did before. It is concluded that the improvement in chest pain limited cardiac performance after bypass surgery is well correlated with the improvement in myocardial aerboic metabolism.     

Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

Aim: During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before and during leg exercise. Material and methods: Eight healthy male subjects were investigated twice in the fasting state: during 3 h infusion of octreotide [30 ng (kg min)^?1] or sodium chloride with exercise at 50% of maximal VO₂ in the last hour. Glucose uptake and oxygen uptake in the leg were measured using Fick’s principle by blood sampling from an artery and a femoral vein. Blood flow in the leg was measured using the indicator (indocyanine green) dilution technique. Results: After an initial decrease during rest, octreotide infusion resulted in a significant increase in arterial glucose concentrations compared to control conditions during exercise (mean ± SEM: 7·6 ± 0·6 versus 5·6 ± 0·1 mmol l^?1, P<0·01). During rest, octreotide did not change the leg glucose uptake (59 ± 10 versus 55 ± 11 μmol min^?1). In contrast, leg glucose uptake was significantly lower during exercise compared to control conditions (208 ± 79 versus 423 ± 87 μmol min^?1, P<0·05). During exercise, leg oxygen uptake was not different in the two experiments (20·4 ± 1·3 versus 19·5 ± 1·1 μmol min^?1). Conclusion: In conclusion, infusion of octreotide reduced leg glucose uptake during exercise, despite the same leg oxygen consumption and blood flow compared to control conditions. The hyperglycaemic effect of octreotide can partly be explained by the reduction in leg glucose uptake. Furthermore, the results suggest that a certain level of circulating insulin is necessary to obtain sufficient stimulation of glucose uptake in the exercising muscles.     

大鼠严重烧伤早期心肌营养性血流与能量负荷变化

为探讨烧伤后心肌损害的发病机制，测定了大鼠严重烧伤早期心肌能量负荷（ＥＣ）及心肌营养性血流（ＮＢＦ）的变化。实验结果：烧伤后１小时心肌ＮＢＦ即明显下降（３．８３％±０．１７％，Ｐ＜０．０１，对照值为５．００％±０．１５％），伤后１２小时降至最低（１．９７％±０．１０％，Ｐ＜０．０１），伤后２４小时仍明显低于对照值（３．７６％±０．１４％，Ｐ＜０．０１）。随着心肌ＮＢＦ的迅速下降，心肌高能磷酸化合物ＡＴＰ、ＡＤＰ迅速大幅度降低，心肌ＥＣ于伤后３小时开始明显下降（０．７５±０．０３，Ｐ＜０．０１，对照值为０．８４±０．０２），以伤后１２小时最低（０．４９±０．０９，Ｐ＜０．０１），至２４小时尚未恢复到对照水平（０．６０±０．０８，Ｐ＜０．０１）。心肌ＥＣ的降低与ＮＢＦ的减少呈显著正相关（ｒ＝０．８２３９，Ｐ＜０．０１）。结果提示：烧伤早期心肌即发生血液灌流不足，心肌能量代谢障碍，这可能是烧伤早期心肌细胞损伤的重要原因之一。     

Effects of prostaglandin-E1 on ST segment elevation and regional myocardial blood flow during experimental myocardial ischaemia in dogs

Abstract. The effects of prostaglandin E₁ (PGE₁) on myocardial ischaemia (as measured by epicardial ST segment changes), myocardial flow and substrate exchange has been studied in dogs. Myocardial ischaemia was induced by intermittent external clipping of a branch of the left anterior descending coronary artery.
During occlusion with a continuous intravenous infusion of isoprenaline, elevated epicardial ST segments (∑ST), were raised to 46 ± 6 mV (mean ± SEM). Pretreatment with PGE₁ reduced ∑ST to 34 ± 6 mV ( P <0.001), but had no effect on mean aortic blood pressure (AP¯) or on regional myocardial blood flow. Isoprenaline infusion increased plasma free fatty acids (FFA) to 1925 ± 150 μmol/l and this was reduced to 1320 ± 220 μmol/l by PGE₁ ( P <0.005).
During occlusion without isoprenaline, PGE₁ did not effect ∑ST or plasma FFA when infused intravenously or into the left atrium. Mean aortic blood pressure decreased from 131 ± 7 to 108 ± 10 (PGE₁ i.v.) or 109 ± 8 mmHg (PGE₁ i.a.) ( P <0.001). This was associated with a decrease in regional myocardial blood flow, both in the ischaemic and non-ischaemic myocardium. However, when blood pressure was maintained constant, intravenous PGE₁ tended to decrease occlusion-induced ST segment elevation.
These results suggest that PGE₁ can reduce isoprenaline-stimulated myocardial ischaemia through its antilipolytic action but in the absence of catecholamine stimulation the main effect is to reduce blood pressure thereby counterbalancing any potentially beneficial effects on the ischaemic myocardium.     

Free fatty acids exert a greater effect on ocular and skin blood flow than triglycerides in healthy subjects

BACKGROUND: Free fatty acids (FFAs) and triglycerides (TGs) can cause vascular dysfunction and arteriosclerosis. Acute elevation of plasma FFA and TG concentration strongly increase ocular and skin blood flow. This study was designed to discriminate whether FFA or TG independently induce hyperperfusion by measuring regional and systemic haemodynamics. METHODS: In a balanced, randomized, placebo-controlled, double-blind, three-way, crossover study nine healthy subjects received either Intralipid (Pharmacia and Upjohn, Vienna, Austria) with heparin, Intralipid alone or placebo control. Pulsatile choroidal blood flow was measured with laser interferometry, retinal blood flow and retinal red blood cell velocity with laser Doppler velocimetry, and skin blood flow with laser Doppler flowmetry during an euglycaemic insulin clamp. RESULTS: A sevenfold increase of FFA during Intralipid/heparin infusion was paralleled by enhanced choriodal, retinal, and skin blood flow by 17 +/- 4%, 26 +/- 5% (P < 0.001), and 47 +/- 19% (P = 0.03) from baseline, respectively. In contrast, a mere threefold increase of FFA by infusion of Intralipid alone did not affect outcome parameters, despite the presence of plasma TG levels of 250-700 mg dL(-1); similar to those obtained during combined Intralipid/heparin infusion. Systemic haemodynamics were not affected by drug infusion. CONCLUSIONS: Present findings demonstrate a concentration-dependent increase in ocular and skin blood flow by FFA independently of elevated TG plasma concentrations. As vasodilation of resistance vessels occur rapidly, FFA may play a role in the development of continued regional hyperperfusion and deteriorate microvascular function.     

Alpha-adrenoceptor subtypes and regional myocardial blood flow distribution during coronary occlusion in dogs

The involvement of postsynaptic alpha-adrenoceptors in the distribution of regional myocardial blood flows (RMBFs, microsphere technique) within the left ventricle has been investigated during intermittent coronary artery occlusion in open-chest anesthetized dogs. Two types of RMBFs distribution were assessed: (1) between endocardial (endo) and epicardial (epi) layers (endo/epi ratio) and (2) between nonischemic (NIZ) and ischemic zones (IZ) (IZ/NIZ ratio). Equipressor does of selective alpha 1-(cirazoline after rauwolscine) and alpha 2-(UK-14,304 after prazosin) adrenoceptor agonists were infused in dogs previously submitted to ganglionic and muscarinic blockade. In a control group, aortic pressure was mechanically raised by aortic stenosis to levels similar to those reached with both alpha-adrenoceptor agonists. Cirazoline and aortic stenosis increased RMBFs in IZ and NIZ but did not alter the calculated coronary resistance in NIZ and did not affect endo/epi and IZ/NIZ ratios. In contrast, UK-14,304 preferentially augmented coronary resistance in NIZ, increased IZ/NIZ ratio (both P less than 0.05) but did not affect endo/epi ratio in IZ and NIZ. Thus, we conclude that if transmural distribution of RMBFs (endo/epi ratio) is not preferentially controlled by any alpha-adrenoceptor subtype, postsynaptic alpha 2-adrenoceptors are of importance during coronary occlusion in promoting a favorable redistribution of RMBFs from NIZ towards IZ by inducing a selective NIZ coronary vasoconstriction (ie a "reverse coronary steal").     

Effects of pacing rates on global and regional myocardial blood flow

Background: Information is scarce on the effects of right ventricular apical (RVA) pacing on regional and global myocardial blood flow (MBF). The purpose of this study was to assess the relationship between pacing rate and both regional and global MBF. Methods: Four patients with exclusive atrial pacing and six patients with exclusive RVA pacing underwent three consecutive H₂¹⁵O positron emission tomography scans at 60, 90, and 130 pulses per minute (ppm). For each pacing rate, regional and global MBF was determined. In all patients, the left ventricular (LV) function was normal. Results: By varying the atrial pacing rate from 60 to 130 ppm, the mean global MBF increased from 0.94 to 1.40 mL/g/min, whereas the mean septal to lateral MBF ratio decreased from 1.09 to 0.83. In ventricular‐paced patients at corresponding rates, the mean global MBF also increased from 1.07 to 1.52 mL/g/min but here the mean septal to lateral MBF ratio increased from 0.83 to 1.0. Conclusions: During both acute atrial and RVA pacing, regional and global MBF increases with higher pacing rates. However, the septal to lateral MBF ratio decreases with atrial pacing and increases with RVA pacing in patients with normal LV function. In RVA pacing, these different rate‐dependent effects on regional MBF can be considered as a favorable factor that helps to understand why in some long‐term paced patients, LV function is preserved. (PACE 2011; 34:587–592)     

Haemodynamics and myocardial metabolism of phosphorus depleted dogs: effects of catecholamines and angiotensin II

The responses of arterial pressure and myocardial contractile force (VPM) to infusion of angiotensin II, noradrenaline and orciprenaline were examined in twelve dogs during a control phase, after 30 days of dietary phosphorus deprivation and after 21 days of phosphorus repletion. In the phosphorus depletion period, animals had low skeletal and heart muscle Pi content, low magnesium, ATP and creatine phosphate in skeletal and heart muscle with no change of ADP, AMP or energy charge. In the basal state, VPM was diminished with no change of end-diastolic and systolic pressure. Infusion of angiotensin II caused a significantly smaller rise of arterial pressure (angiotensin II resistance), and the stimulatory effect of noradrenaline and orciprenaline on VPM was diminished (catecholamine resistance). These effects were reversible with Pi repletion. In phosphorus depletion, arterial concentrations were increased for lactate, unchanged for FFA and decreased for acetoacetate/beta-hydroxybutyrate. Unchanged myocardial extraction of lactate or beta-hydroxybutyrate and preserved cell Pi uptake for glycogenolysis were observed. The initial rate of uptake of calcium and concentrating ability of myocardial sarcoplasmic reticulum were unchanged.     

Fibrinolysis in a lipid environment: modulation through release of free fatty acids

BACKGROUND: Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, but the structure of clots in vivo includes additional constituents (proteins, phospholipids) that modulate their solubilization. OBJECTIVE: We examined the presence of free fatty acids in thrombi and their effects on distinct stages of fibrinolysis (plasminogen activation, plasmin activity). METHODS AND RESULTS: Using the fluorescent probe acrylodated intestinal fatty acid-binding protein, variable quantities (up to millimolar concentrations) of free fatty acids were demonstrated in surgically removed human thrombi. Oleic acid at relevant concentrations reversibly inhibits more than 90% of the amidolytic activity of plasmin on a synthetic substrate (Spectrozyme PL), but only partially inhibits its fibrinolytic activity measured using turbidimetry. Chromogenic assays detecting the generated plasmin activity show that plasminogen activation by tissue-type plasminogen activator (t-PA) is completely blocked by oleic acid in the fluid phase, but is accelerated on a fibrin matrix. A recombinant derivative of t-PA (reteplase) develops higher fibrin specificity in the presence of oleic acid, because both the inhibition of plasminogen activation in free solution and its enhancement on fibrin template are stronger than with wild-type t-PA. CONCLUSION: Through the stimulation of plasminogen activation on a fibrin template and the inhibition of plasminogen activators and plasmin in the fluid phase, free fatty acids confine the action of fibrinolytic proteases to the site of clotting, where they partially oppose the thrombolytic barrier function of phospholipids.     

Platelet glycoprotein IIb-IIIa and size are increased in acute myocardial infarction

Abstract. Platelet aggregation, which plays an important role in acute myocardial infarction (AMI), is mediated by fibrinogen binding to the platelet membrane glycoprotein (GP)^IIb-IIIa (CD41). This study measured the relative number of GPIIb-IIIa complexes on platelets from patients immediately following AMI ( n = 14) compared with those from controls ( n = 14). Flow cytometry was used to demonstrate that there were, on average, 20% more GPIIb-IIIa complexes on platelets after AMI compared with controls. Platelet size was also 7% greater in AMI and it is known that larger platelets are more reactive. Since platelet size and protein content are determined at thrombopoiesis the majority of these platelets must have been circulating prior to AMI. Larger platelets, with more GPIIb-IIIa may, therefore, be causally related to AMI.     

Association between increased concentrations of free thyroxine and unsaturated free fatty acids in non-thyroidal illnesses: role of albumin

We measured the concentrations of non-esterified free fatty acids and free and total thyroid hormones in serum from patients with various non-thyroidal illnesses (NTI) and chronic renal failure (CRF). The total concentration of free fatty acids was measured enzymatically and the eight most abundant fractions were determined by gas-liquid chromatography. The concentration of total free fatty acids was significantly increased in the NTI group as compared with controls (p less than 0.01); the concentrations of oleic, linoleic and linolenic acid were increased more than those of the other fractions. In NTI the serum-free thyroxine (FT4) concentration was increased (p less than 0.01) and the free triiodothyronine (FT3) concentration was decreased (p less than 0.001); these concentrations were measured by equilibrium dialysis. There was a significant correlation between the levels of total free fatty acids and FT4 in the NTI (n = 43) group (r = 0.45, p less than 0.01), and also between the levels of linoleic acid and FT4 (r = 0.35, p less than 0.05). The serum albumin concentration was decreased in the NTI group, and when free fatty acid to albumin molar ratios were calculated stronger correlations with FT4 were observed (total free fatty acids: r = 0.55; p less than 0.001; oleic acid: r = 0.30, p less than 0.05; linoleic acid: r = 0.46, p less than 0.01; linolenic acid: r = 0.35, p less than 0.05). There was no correlation between FT4 and unsaturated FFA concentrations in CRF patients, who had normal mean FT4 and total FFA levels. These results support the hypothesis that unsaturated fatty acids are involved in the increase of serum FT4 in NTI, especially when albumin levels are low.