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Biomedical subjects

J D Folts

Publications and source records attributed to J D Folts.

At least 37 records · Page 2Linked to original sources
PubMed1995

Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries.

BACKGROUND: Moderate daily consumption of alcoholic beverages is a negative risk factor for the development of atherosclerosis and coronary artery disease (CAD), especially in France and other Mediterranean areas where red wine is regularly consumed with meals. Platelets contribute to the development of atherosclerosis, CAD, and acute arterial thrombus formation. METHODS AND RESULTS: Anesthetized dogs were prepared with the Folts model of mechanically stenosed coronary arteries and intimal damage. Periodic acute platelet-mediated thrombus formation occurred, causing cyclic flow reductions (CFRs) in coronary blood flow. The CFRs were eliminated by the administration of 1.62 +/- 1.12 mL/kg red wine intravenously (IV) and 4.0 mL/kg intragastrically (IG). The CFRs were abolished by 2.04 +/- 1.42 mL/kg of grape juice IV and 10 mL/kg IG. White wine did not have significant results in eliminating the CFRs, either IV (2.0 mL/kg) or IG (4.0 mL/kg), decreasing the slopes of the CFRs only slightly. CONCLUSIONS: Pure ethanol has been shown to inhibit platelet aggregation in vitro, ex vivo, and in vivo, although a blood alcohol content (BAC) of > or = 0.2 g/dL is usually required. The BAC of dogs administered the red wine-saline solution intravenously was 0.028 g/dL, much less than is usually necessary for platelet inhibition with pure ethanol. Because red wine and grape juice, but not white wine, abolished the CFRs, this suggests there are compounds present in red wine and grape juice that are not present or are present in a lower concentration in white wine. Wine and grape juice contain a wide variety of naturally occurring compounds, including fungicides, tannins, anthocyanins, and phenolic flavonoids (including flavonols and flavones). These compounds have shown platelet inhibition in vitro by a variety of proposed mechanisms. Perhaps the biological activity of these compounds can explain the platelet-inhibitory properties of red wine and grape juice that are observed without high levels of ethanol.

Animals↗
PubMed1995

Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.

Endothelium-derived relaxing factor is important for vascular homeostasis and possesses qualities that may modulate vascular injury, including vasodilation, platelet inhibition, and inhibition of smooth muscle proliferation. S-nitrososerum albumin is a naturally occurring adduct of nitric oxide (NO) with a prolonged biologic half-life and is a potent vasodilator and platelet inhibitor. Given the avidity of serum albumin for subendothelial matrix and the antiproliferative effects of NO, we investigated the effects of locally delivered S-nitroso-bovine serum albumin (S-NO-BSA) and a polythiolated form of bovine serum albumin (pS-BSA) modified to carry several S-nitrosothiol groups (pS-NO-BSA) on neointimal responses in an animal model of vascular injury. Locally delivered S-NO-BSA bound preferentially to denuded rabbit femoral vessels producing a 26-fold increase in local concentration compared with uninjured vessels (P = 0.029). pS-NO-BSA significantly reduced the intimal/medial ratio (P = 0.038) and did so in conjunction with elevations in platelet (P < 0.001) and vascular cGMP content (P < or = 0.001). pS-NO-BSA treatment also inhibited platelet deposition (P = 0.031) after denuding injury. Comparison of BSA, S-NO-BSA, pS-NO-BSA, and control revealed a dose-response relationship between the amount of displaceable NO delivered and the extent of inhibition of neointimal proliferation at 2 wk (P < or = 0.001). Local administration of a stable protein S-nitrosothiol inhibits intimal proliferation and platelet deposition after vascular arterial balloon injury. This strategy for the local delivery of a long-lived NO adduct has potential for preventing restenosis after angioplasty.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Densitometric assessment of regional left ventricular systolic function during graded ischemia in the dog by use of dual-energy digital subtraction ventriculography.

Densitometric analysis of images obtained by digital subtraction angiography (DSA) allows for more reproducible and less operator-dependent quantitation of ventricular function. Conventional DSA uses temporal subtraction but is limited by misregistration artifacts. Dual-energy digital subtraction angiography (DE-DSA) is immune to such misregistration artifacts. The ability of DE-DSA to quantitate changes in regional ventricular volume resulting from ischemia was tested. Densitometric analysis of both phase-matched and ejection fraction DE-DSA images was used to quantitate regional left ventricular systolic function during four levels of ischemia ranging from mild to severe in open-chest dogs (n = 10). DE-DSA left ventriculograms were obtained by means of central venous injections of iodinated contrast medium. Ischemia was graded according to percentage of systolic wall thickening as measured by sonomicrometry. Phase-matched end-systolic images were obtained at each of four levels of ischemia by subtracting an end-systolic control image from each end-systolic ischemic image. Ejection fraction images were obtained at the control level and at each level of ischemia by subtracting an end-systolic image from an end-diastolic image of the same cardiac cycle. The resulting wall motion difference signals represent the changes in regional ventricular volumes and were quantitated by densitometry. Densitometry was able to detect the effect of all levels of ischemia on regional function, even the mildest. Densitometric analysis of both phase-matched and ejection fraction DE-DSA images provides a sensitive technique for detecting and quantitating the changes in regional left ventricular systolic volume that occur with ischemia.

Angiography, Digital Subtraction↗
PubMed1993

High-dose droperidol protects against experimental coronary thrombosis in dogs and pigs and attenuates aggregation of porcine platelets and Ca2+ mobilization in human platelets.

BACKGROUND: Activation of platelets after contact with thrombogenic substrates may be an early factor leading to coronary artery thrombosis and myocardial infarction. Haloperidol, a butyrophenone, possesses weak in vitro platelet inhibitory activity. Experiments were designed to determine whether droperidol, a butyrophenone adjunct to anesthesia, protected against experimental coronary thrombosis in intravenously anesthetized open-chest dogs and pigs, attenuated ex vivo porcine platelet aggregation, and inhibited agonist-induced increases in [Ca2+]i in human platelets. METHODS: In dogs and pigs, a lesion consisting of deendothelialization, deep vessel wall injury, and critical stenosis was created in the proximal circumflex arteries, resulting in coronary thrombus formation accompanied by decreased circumflex artery blood flow. Embolization of the thrombus restored flow, but the cycle then repeated, resulting in repetitive cyclical flow reductions (CFRs). These were measured using an electromagnetic flow probe. RESULTS: In dogs, droperidol 0.2 mg/kg intravenous rapidly abolished CFRs in all ten animals, with frequency decreasing from 0.22 +/- 0.01 cycles/min to 0. Droperidol 0.8 mg/kg intravenous rapidly abolished CFRs in seven of eight pigs, with frequency decreasing from 0.15 +/- 0.01 to 0.02 cycles/min (P < 0.005). In both species, additional doses of droperidol were effective against CFRs augmented with intravenous epinephrine, a catecholamine that stimulates thrombosis. Ex vivo platelet aggregation studies were performed in platelet-rich plasma obtained from pigs before and after droperidol 0.8 mg/kg intravenous. Pretreatment with the drug resulted in marked inhibition of aggregation evoked by collagen, modest attenuation of that elicited by adenosine diphosphate (ADP), but no effect on that evoked by arachidonic acid. In human platelets, apparent [Ca2+]i was estimated using the fluorescent indicator indo-1 and flow cytometry. Droperidol 10(-7), 10(-6), and 10(-5)M had a dose-dependent inhibitory effect on the amplitude of increases in [Ca2+]i evoked by 10(-5)M serotonin (plus 10(-7)M epinephrine). The higher droperidol concentration decreased the response to as much as 30% of control (P < 0.001). Droperidol lacked effect on Ca2+ mobilization elicited with 10(-6)M ADP. CONCLUSIONS: The results from three experimental models indicate that droperidol attenuates experimental coronary thrombosis in animals and suggest that this inhibition may result, in part, from a direct droperidol depressant effect on platelet activation and aggregation.

Adenosine Diphosphate↗
PubMed1993

Sodium nitroprusside, an endothelium-derived relaxing factor congener, increases platelet cyclic GMP levels and inhibits epinephrine-exacerbated in vivo platelet thrombus formation in stenosed canine coronary arteries.

Sodium nitroprusside (SNP), a nitrosovasodilator, increases platelet cyclic GMP levels and inhibits platelet activity in vitro. The antiplatelet properties of SNP are not well established in vivo, however, and consequently are not appreciated by clinicians. In our established model of mechanically stenosed canine coronary arteries (MSCA) with intimal damage, periodic acute platelet thrombus formation (APTF) occurs, followed by embolization distally, which then causes cyclic flow reductions (CFRs) in coronary blood flow. Aspirin (ASA) abolished platelet-mediated CFRs in our model, but they recur when epinephrine (EPI) is infused (0.2 microgram/kg/min). SNP was given continuously intravenously (i.v.) to 17 dogs with MSCA; CFRs were abolished in all dogs by SNP at 4.4 +/- 2.7 micrograms/kg/min (mean +/- SD). Mean arterial blood pressure (MAP) decreased by 19 +/- 9 mm Hg (p < 0.001) from control, while heart rate (HR) increased 35 +/- 20 beats/min (p < 0.001). Platelet cyclic GMP levels were 2.9 +/- 1.1 pmol/10(8) platelets before SNP infusion, and increased to 4.3 +/- 1.6 pmol/10(8) platelets (p < 0.05) when CFRs were abolished. CFRs were not renewed during the continued SNP infusion when EPI was infused at 0.2 microgram/kg/min for 20 min in 11 dogs, but CFRs returned within 5-25 min after the SNP infusion was terminated. The return of CFRs occurred together with a decrease in platelet cyclic GMP levels to 3.3 +/- 1.4 pmol/10(8) platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Continuous measurement of left ventricular performance during and after maximal isometric deadlift exercise.

BACKGROUND: Isometric exercise produces a reflex increase in arterial blood pressure that is proportional to the intensity and mass of muscle used during contraction. Little is known about the transient effects of heavy weight lifting on left ventricular performance. In this study, we measured continuous changes in left ventricular performance during maximal large-muscle isometric exercise using the standing deadlift position. METHODS AND RESULTS: Ten healthy young men performed serial deadlifts at 50% of maximal voluntary effort for 90 seconds and 100% of maximal effort for 30 seconds. Echocardiographic imaging (apical four-chamber view), arterial blood pressure (brachial artery catheter), and electrocardiographic monitoring were recorded throughout the deadlift and for 30 seconds of recovery. Aortic flow velocity was also monitored during a separate series of deadlifts. During 100% maximal deadlift, mean arterial pressure increased from 108 +/- 4 to 164 +/- 6 mm Hg. Left ventricular ejection fraction declined initially (from 57 +/- 2% to 49 +/- 3%) at 15 seconds into the lift and recovered (56 +/- 1%) due to significant increases in end-diastolic volume (104 +/- 11 ml to 132 +/- 16 ml) by the end of the lift. The peak systolic pressure/end-systolic volume ratio did not change during the deadlift. After cessation of the deadlift, mean arterial pressure declined precipitously (to 88 +/- 4 mm Hg) within 5 seconds and gradually returned to baseline after 30 seconds. Left ventricular performance indexes all increased significantly during the recovery phase (ejection fraction to 68 +/- 3%, peak systolic pressure/end-systolic volume ratio to 5.9 +/- 0.9). Findings were qualitatively similar for the 50% deadlift. CONCLUSIONS: During an intense isometric deadlift, left ventricular performance declines initially but is restored by the Frank-Starling mechanism. Upon release of the deadlift, increased left ventricular performance develops in conjunction with a rapid decrease in arterial pressure. The combined effects of increased wall stress during the lift phase and enhanced contractility during the release phase probably contribute to left ventricular hypertrophy associated with repetitive weight training.

Adult↗
PubMed1991

Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries.

BACKGROUND: Nitroglycerin and other clinically relevant organic nitrate derivatives have been shown to inhibit platelet aggregation in vitro. This antithrombotic effect of nitrates is potentiated by reduced thiol. To determine the potential relevance of this mechanism of action in vivo, we examined the effect of intravenous nitroglycerin infusion on periodic platelet thrombus formation in a canine model of coronary artery stenosis. METHODS AND RESULTS: We used a canine model of coronary artery stenosis associated with cyclic reductions in coronary blood flow that have been shown to depend on periodic platelet thrombus formation. We quantified the frequency of cycles per 40-minute observation period and monitored the effect of a continuous infusion of intravenous nitroglycerin on the cycle frequency. The administration of 10-15 micrograms/kg/min nitroglycerin reduced cyclic platelet thrombus formation significantly and did so without a significant change in coronary artery blood flow. Pretreatment with the reduced thiol, N-acetylcysteine (100 mg/kg during 30 minutes), led to inhibition of cyclic platelet thrombus formation by intravenous nitroglycerin at doses that alone had no such effect (5 micrograms/kg/min). CONCLUSION: These data suggest that one mechanism by which intravenous nitroglycerin improves ischemia in acute coronary artery disease syndromes may be by inhibition of platelet thrombus formation and may highlight the potential importance of reduced thiol in this mechanism.

Acetylcysteine↗
PubMed1991

Geometric quantitative coronary arteriography. A comparison of unsubtracted and dual energy-subtracted images.

The application of dual energy (DE) subtraction techniques to quantitative coronary arteriography (QCA) has the advantage of removing the tissue signal surrounding the vessel profile. We have compared the performance of two geometric QCA algorithms on DE-subtracted and -unsubtracted images to determine, for each, if DE subtraction is advantageous. The two algorithms under study were an edge detection algorithm and a Fourier analysis-based algorithm. For each algorithm, linear regression analysis was performed of measured cross-sectional area (CSA) versus actual CSA of coronary vessel phantoms. The edge detection algorithm was found to have improved precision (P less than .05) when applied to the DE-subtracted images. The Fourier analysis algorithm, however, was not effected by the DE subtraction. Among the unsubtracted image results, the Fourier measurements were more accurate (P less than .05) than the edge detection measurements. We conclude that the benefits to edge detection QCA of DE tissue subtraction outweigh the disadvantages of increased image noise and possible misregistration artifacts. However, the Fourier algorithm is relatively insensitive to tissue signal variations.

Algorithms↗
PubMed1990

Aspirin and dipyridamole and their limitations in the therapy of coronary artery disease.

We have reviewed some of the voluminous literature on the effects of aspirin combined with dipyridamole on coronary thrombosis. There is clear evidence that aspirin is partially effective in preventing platelet aggregation and subsequent thrombosis in experimental constricted and damaged coronary arteries of dogs. Clinical studies show a clear reduction in myocardial infarction in male human subjects who are given aspirin as therapy for unstable angina, or as prophylaxis in asymptomatic individuals. In many studies aspirin and dipyridamole have been combined and are effective. We have not found dipyridamole to be effective in the dog with coronary artery constriction and find no substantial evidence that it is effective in preventing myocardial infarction in man. Until definitive studies show that combining dipyridamole with aspirin is more effective than aspirin alone, we do not recommend its use for prevention of coronary thrombosis.

Animals↗
PubMed1990

Effects of cigarette smoke and nicotine on platelets and experimental coronary artery thrombosis.

The causal link between smoking, atherosclerosis and an increased risk for acute platelet mediated coronary events such as acute platelet thrombus formation, myocardial infarction, and sudden coronary death is not clear. Our studies suggest that there may be a transient increase in in vivo platelet activity with each exposure to cigarette smoke or elevated plasma nicotine. It is thought that platelets may contribute to the acceleration of the atherosclerotic process by several mechanisms (5). Thus it may be that each time a person increases their platelet activity, by smoking or some other means, and given other predisposing conditions such as elevated lipids and/or acute intimal damage, such as rupture of an atherosclerotic plaque, the atherosclerotic process may be enhanced. In addition it appears that cigarette smoke makes a developing thrombus more adherent and less likely to embolize distally, although the effect is transient. Finally, cigarette smoke may provide the final stimulus for an occlusive coronary thrombus in a stenosed coronary artery already predisposed to thrombosis by other risk factors. This may account for the fact that the risk of coronary occlusion and myocardial infarction decreases markedly in the first year after quitting (65). It may be that smoking has a greater likelihood of precipitating a fatal thrombus than it does of accelerating the altherosclerotic process. This would be reflected in the inability of aspirin to prevent the smoking induced enhancement of CFR's in our model (23) or the enhancement of platelet function in men with coronary artery disease (66).

Animals↗
PubMed1990

Combined inhibitory effects of aspirin and ethanol on adrenaline exacerbation of acute platelet thrombus formation in stenosed canine coronary arteries.

STUDY OBJECTIVE: This study was performed to see whether ethanol could potentiate the inhibitory effect of aspirin on recurrent platelet thrombus formation and subsequent embolisation, which have been shown to cause cyclic reductions in blood flow in 70% of mechanically stenosed dog coronary arteries. DESIGN: After mechanical stenosis of the circumflex coronary artery in open chest dogs, cyclic variations in blood flow were measured during treatment with aspirin, ethanol, or both. SUBJECTS: 20 adult mongrel dogs were used: in group 1 (n = 5) each dog was given aspirin 5 mg.kg-1; in group 2 (n = 5) each was given 1.2 ml.kg-1 ethanol; in group 3 (n = 10) each was given aspirin 1 mg.kg-1 combined with either 0.3 or 0.6 ml.kg-1 ethanol. MEASUREMENTS AND MAIN RESULTS: In group 1, aspirin 5 mg.kg-1 abolished cyclic reductions in circumflex blood flow, but an intravenous infusion of adrenaline (0.4 microgram.kg-1.min-1 for 15 min) caused them to return. In group 2, ethanol 1.2 ml.kg-1 abolished cyclic flow reductions but they returned after adrenaline infusion challenge. In group 3, aspirin 1 mg.kg-1 combined with either 0.6 or 0.3 mg.kg-1 ethanol abolished cyclic flow reductions and protected against their return during adrenaline infusion challenge in 9/10 dogs. CONCLUSIONS: The results suggest that ethanol potentiates the inhibitory effects of aspirin on platelet thrombus formation in our model of simulated coronary artery disease.

Animals↗
PubMed1990

Inhibition of acute platelet thrombosis formation in stenosed canine coronary arteries by specific serotonin 5HT2 receptor antagonist ritanserin.

STUDY OBJECTIVE: The aim of the study was to test the hypothesis that platelet serotonin 5HT2 receptors are important in the genesis of thrombosis in stenosed coronary arteries. DESIGN: The specific serotonin 5HT2 receptor antagonist, ritanserin was used as a pharmacological tool to examine the effect of removal of the participation of the 5HT2 receptors on thrombus growth, in a paired statistical design. EXPERIMENTAL MATERIAL: The study involved 10 open chest anaesthetised dogs, with constrictors of critical diameter applied to the left circumflex coronary artery. MEASUREMENTS AND MAIN RESULTS: Blood flow was monitored in the left circumflex coronary arteries, distal to the critical stenosis. Flow reductions occurred that have previously been shown to be caused by the accumulation of platelet thrombi. By embolising the thrombi, the process could be monitored cyclically (cyclic flow reductions). The specific serotonin 5HT2 receptor antagonist, ritanserin, abolished cyclic flow reductions at a dose of 0.5 mg.kg-1. There was no effect on blood pressure or heart rate on administration of ritanserin at any dose. The serotonin blockade by ritanserin also prevented the reestablishment of cyclic flow reductions by adrenaline infusion (0.4 micrograms.kg-1.min-1), but required ritanserin doses up to 1.5 mg.kg-1. Ex vivo aggregation of platelets was reduced in blood taken from the dogs after ritanserin administration. CONCLUSIONS: These results constitute further evidence of the possible importance of serotonin as a mediator of platelet thrombosis in stenosed coronary arteries.

Animals↗
PubMed1990

Quantitative dual-energy coronary arteriography.

Subtraction techniques for digital cardiac imaging have been hampered by misregistration artifacts. The use of dual-energy imaging is being evaluated as a means for reducing these artifacts. Results reported previously indicate that the dual-energy technique may be useful for applications such as exercise ventriculography and general quantification tasks. The purpose of the current study is to investigate the use of dual-energy subtraction imaging for quantitative coronary arteriography. In vivo coronary vessel phantoms (0.2 to 7 mm2 in cross-sectional area) were used to study the potential advantages of tissue suppressed energy subtracted images over unsubtracted images for quantification of absolute vessel cross-sectional area when cardiac motion is present. Estimates of lumen cross-sectional area (N = 20) were determined using videodensitometric analysis of selected energy subtracted and unsubtracted images. Linear regression analysis of measured and actual cross-sectional area showed energy subtracted image data (slope = 1.06, intercept = 0.48 mm2, r = 0.99) to have improved accuracy (P less than .05) and precision (P less than .05) over unsubtracted image data (slope = 1.24, intercept = 1.07 mm2, r = 0.95).

Angiography, Digital Subtraction↗
PubMed1990

Exacerbation of acute platelet thrombus formation in stenosed dog coronary arteries with smoke from a non-tobacco-burning cigarette.

The tobacco industry proposes to release a "new" cigarette with a burning charcoal tip, which heats the tobacco as air is drawn through it and into the lungs of the smoker. It is claimed to be safer because the tobacco does not burn. Using our established canine model of coronary artery stenosis with moderate intimal damage, we compared this new cigarette (0.4 mg nicotine) with a regular cigarette by ventilating dogs (n = 10) with room air and then either new or regular smoke (two cigarettes over about 10 minutes). In our dog model, periodic acute platelet thrombus formation followed by embolization produced cyclical flow reductions in coronary blood flow where the rate of flow decline was proportional to the degree of in vivo platelet-vessel wall interaction. The rate of flow decline increased from -4.81 +/- 1.29 ml/min2 to -9.60 +/- 2.29 ml/min2 after ventilation with the new-type smoke (p less than 0.01). Similarly, the rate of flow decline increased from -5.43 +/- 1.28 ml/min2 to -9.28 +/- 2.31 ml/min2 after ventilation with regular cigarette smoke (p less than 0.01). Despite the lack of a clear causal link between cigarette smoking and the acute manifestations of cardiovascular disease, the data presented here indicate that the new cigarette is just as potent as regular cigarettes at increasing in vivo platelet activity and exacerbating acute platelet thrombus formation in the dog. We conclude that the new proposed non-tobacco-burning cigarette has deleterious effects similar to those of conventional cigarettes, and thus does not eliminate smoking as a risk factor in cardiovascular disease in human beings.

Animals↗
PubMed1989

Halothane, but not isoflurane or enflurane, protects against spontaneous and epinephrine-exacerbated acute thrombus formation in stenosed dog coronary arteries.

Occlusive platelet thrombi periodically form in mechanically stenosed dog coronary arteries producing cyclical blood flow reductions occurring over 4-7 min. Cyclical coronary flow reductions are exacerbated by IV epinephrine 0.4 microgram.kg-1.min-1 for 15 min. These flow reductions can be abolished by known inhibitors of platelet function. This study assesses the effect of halothane, isoflurane, and enflurane on spontaneous- and epinephrine-exacerbated cyclical coronary flow reductions. Twenty-three open-chest dogs [1% halothane (n = 5), 0.5% halothane (n = 5), 0.25% halothane (n = 3), 1.5% isoflurane (n = 5), and 2.0% enflurane (n = 5)] with a mechanically stenosed coronary artery showed cyclical blood flow reductions. With 1.0% halothane administration, spontaneous cyclical blood flow reductions were abolished (n = 5), whereas during administration of isoflurane 1.5% (n = 5) and enflurane 2.0% (n = 5) cyclical flow reductions and myocardial ischemia continued. Subsequent administration of halothane in the isoflurane and enflurane groups showed abolition of coronary flow reductions in all animals (n = 10). In eight animals a 15-min epinephrine infusion (0.4 microgram.kg-1.min-1) was given following a control period and again following abolition of coronary flow reductions by halothane 0.5% (n = 5) and halothane 0.25% (n = 3). The magnitude of cyclical blood flow reductions (difference between initial and final coronary flow level of each flow reduction) changed from 52 +/- 11 to 61 +/- 12 ml/min (NS), and frequency increased from 0.37 to 0.57/min (P less than 0.05, n = 8) during epinephrine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗