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Biomedical subjects

J L Mehta

Publications and source records attributed to J L Mehta.

At least 199 records · Page 11Linked to original sources
PubMed1990

Superoxide dismutase decreases reperfusion arrhythmias and preserves myocardial function during thrombolysis with tissue plasminogen activator.

Release of superoxide radicals during the early phase of coronary reperfusion may result in degradation of endothelium-derived relaxing factor (EDRF), extension of myocardial injury, precipitation of arrhythmias, and stimulation of platelet aggregation. These factors may relate to the occurrence of ventricular fibrillation during reperfusion and coronary reocclusion following initial thrombolysis. This study was designed to examine the effects of concomitant administration of superoxide radical scavenger superoxide dismutase (SOD) with tissue plasminogen activator (tPA) compared to tPA alone (without SOD) in acute coronary thrombosis in anesthetized dogs. Dogs with a stable electrically induced coronary thrombus were randomly given intravenously tPA (0.75 mg/kg) alone or SOD bolus (2 mg/kg) followed by SOD (4 mg/kg) + tPA (0.75 mg/kg) over 20 min. tPA alone restored coronary blood flow in six of nine dogs (reperfusion rate of 67%) with time to reflow of 18.5 +/- 6.7 (mean +/- SD) min. Coronary reocclusion occurred spontaneously in four of six dogs with initial reperfusion (reocclusion rate of 67%). In contrast, SOD + tPA restored coronary blood flow in 9 of 12 dogs (reperfusion rate of 75%, not significant vs. tPA alone) with time to reflow of 11.3 +/- 4.8 min and coronary reocclusion occurred in only 3 of 9 dogs with reperfusion (reocclusion rate of 33%, not significant vs. tPA alone). Reperfusion arrhythmias were more frequent in dogs who received tPA alone compared to those who received SOD in addition to tPA (mean Holter-monitored PVC count of 730 vs. 12 beats/h, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Sulfhydryl group in angiotensin converting enzyme inhibitors and superoxide radical formation.

The superoxide radical scavenging effects of the SH group in the captopril molecule has been proposed to be the basis of the "cadioprotective" effect of this angiotensin converting enzyme (ACE) inhibitor in animal models of myocardial injury. We determined the effects of captopril, another ACE inhibitor with an SH group (SQ 26,703), its stereoisomer without ACE inhibitory effect but with an SH group (SQ 14,534), another ACE inhibitor without a SH group (enalaprilat), and N-acetylcysteine on superoxide radical generation by human neutrophils and by the purine-xanthine oxidase reaction. None of the compounds examined decreased superoxide radicals in therapeutic concentrations; however, SH-containing agents directly reduced spectrophotometric absorbance of ferricytochrome C. Thus, SH-containing agents with or without ACE inhibitory effects do not scavenge superoxide radicals.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

TxA2 inhibition and ischemia-induced loss of myocardial function and reactive hyperemia.

To determine the contribution of thromboxane (Tx) A2 release in reperfusion injury, 17 dogs were subjected to total coronary occlusion for 1 h and reperfusion for 1 h. Eleven dogs were treated with saline, and six were treated with selective TxA2 synthetase inhibitor U63,557A (5 mg/kg iv) 30 min before coronary artery occlusion. In all saline-treated dogs, peak reactive hyperemia after 10-s total coronary artery occlusion was diminished (P less than 0.01) after reperfusion. Myocardial segmental shortening was also reduced (9.8 +/- 1.9 to -6.7 +/- 2.0%, P less than 0.01) in the reperfused region. Reperfusion was associated with 737 +/- 343 premature ventricular contractions (PVCs) per hour. Histology revealed extensive myocardial infiltration and capillary plugging by leukocytes in the reperfused region. Myeloperoxidase, an index of leukocyte infiltration, was also increased (P less than 0.02) in the reperfused region. In the U63,557A-treated animals, serum and plasma TxB2 levels were markedly (P less than 0.02) reduced. Decrease in myocardial shortening fraction was less in U63,557A- than in saline-treated animals (P less than 0.05). The frequency of reperfusion PVCs was also significantly reduced (10 +/- 5 PVCs/h, P less than 0.02 compared with saline-treated dogs). However, peak reactive hyperemia was reduced similar to that in saline-treated dogs. Myocardial infiltration and capillary plugging by leukocytes in the reperfused regions was also similar in the U63,557A- and saline-treated dogs. These results indicate that treatment with U63,557A decreases reperfusion arrhythmias and preserves myocardial function. However, coronary reperfusion-induced deterioration in reactive hyperemia is not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Prostacyclin analogue iloprost decreases thrombolytic potential of tissue-type plasminogen activator in canine coronary thrombosis.

Platelets play an important role in the formation of a coronary thrombus and reocclusion after thrombolysis. Therefore, we examined the thrombolytic potential of concomitant intravenous administration of potent platelet inhibitor iloprost, a prostacyclin analogue, with tissue-type plasminogen activator (t-PA; n = 8) and t-PA alone (n = 9) in dogs with an electrically induced occlusive coronary artery thrombus. t-PA (0.75 mg/kg) was given over 20 minutes, and iloprost (4 micrograms/kg) was given over 40 minutes. Reperfusion rate was 63% (five of eight dogs) in the t-PA plus iloprost group and 67% (six of nine dogs) in the t-PA alone group (p = NS). The time to thrombolysis (or reperfusion) in the t-PA plus iloprost group was almost twice as great as in the t-PA alone group (33.0 +/- 13.3 vs. 18.5 +/- 6.7 minutes, mean +/- SD, p less than 0.02), and the duration of reperfusion was much shorter (3.4 +/- 1.8 vs. 39.3 +/- 17.4 minutes, p less than 0.005). Peak coronary artery blood flow after reperfusion in the t-PA plus iloprost group was also less (20 +/- 17 ml/min) than in the t-PA alone group (58 +/- 21 ml/min, p less than 0.005). Reocclusion occurred in all dogs given t-PA with iloprost despite potent synergistic platelet inhibitory effects of t-PA and iloprost, whereas four of six dogs given t-PA alone reoccluded. Neither regimen exerted a significant beneficial effect on regional myocardial shortening during coronary reperfusion. Plasma levels of t-PA were lower when iloprost was given with t-PA (1,022 +/- 360 vs. 1,459 +/- 270 ng/ml in t-PA alone group, p less than 0.05). The detrimental effects of iloprost identified in this study may relate to the reduction in plasma t-PA concentrations by its degradation in the liver caused by the prostacyclin analogue iloprost.

Animals↗
PubMed1990

Superoxide radical-mediated endothelial injury and vasoconstriction of rat thoracic aortic rings.

Endothelium regulates smooth muscle tone in response to various agonists and antagonists by release of vasorelaxing and vasoconstricting factors. It also has been postulated that superoxide radicals, which degrade endothelium-derived relaxing factor, exert smooth muscle-constrictor effects. To determine the role of superoxide radicals on vasomotor tone, we exposed rat thoracic aortic rings in vitro to a superoxide radical-generating system of xanthine and xanthine oxidase (X + XO). In rings with intact endothelium, X + XO caused modest smooth muscle contraction and increased vascular sensitivity to both l-epinephrine and thromboxane A2 (TxA2) "mimic" U46619. These vascular contractile effects were more pronounced in rings without intact endothelium. In the supernates of vascular rings with intact endothelium, TxA2 and prostacyclin metabolites were identified on exposure of vascular rings to X + XO, indicating stimulation of the cyclooxygenase pathway. Although both superoxide radical scavenger superoxide dismutase and cyclooxygenase inhibitor indomethacin blocked release of TxA2 and prostacyclin, only superoxide dismutase blocked the contractile effects of superoxide radicals (p less than 0.05). Neither catalase nor mannitol had any effect on X + XO mediated vasoconstriction, suggesting that hydrogen peroxide and hydroxyl radicals did not participate in the observed effects of X + XO. Exposure of vascular rings to X + XO revealed extensive endothelial disruption as determined by scanning electron microscopy. Thus superoxide radicals exert procontractile effects on vascular smooth muscle and enhance its response to l-epinephrine and TxA2 mimic. These effects are probably exerted by injury to the endothelial barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Comparative platelet inhibitory effects of human neutrophils and lymphocytes.

The effects of isolated leukocytes (polymorphonuclear leukocytes [PMNLs] or neutrophils and lymphocytes) on platelet aggregation in platelet-rich plasma (PRP) were examined. Both PMNLs and lymphocytes decreased platelet aggregation in a concentration-dependent fashion. PMNL-induced, but not lymphocyte-induced, inhibition of platelet aggregation was more pronounced as the incubation time of PRP with PMNLs was prolonged. The platelet-inhibitory effect of PMNLs was enhanced by superoxide dismutase (SOD) and was attenuated by oxyhemoglobin and methylene blue. These agents, in contrast, had no effect on lymphocyte-mediated inhibition of platelet aggregation. Adenosine deaminase did not modulate the platelet inhibitory effects of either PMNLs or lymphocytes. The incubation of PMNLs with PRP was associated with an increase in cyclic guanine 5' monophosphate (cGMP) levels in PRP. Incubation of lymphocytes, however, did not result in an increase in cGMP levels in PRP. Neither PMNLs nor lymphocytes in PRP caused a reduction in thromboxane B2 (TXB2) or an increase in 6-keto-PGF1 alpha. Thus this study shows potent inhibitory effects of isolated PMNLs mediated by a substance with biologic characteristics of nitric oxide. However, the mechanism of lymphocyte-induced inhibition of platelets appears to be independent of prostaglandins, nitric oxide, or adenosine.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Tissue plasminogen activator and plasmin independently decrease human neutrophil activation.

Tissue-plasminogen activator (t-PA) and plasmin both decrease platelet aggregation, which may contribute to thrombolysis and tissue salvage. Since neutrophils may contribute to reperfusion injury, we examined the effects of t-PA and plasmin on human neutrophil function. t-PA (1 to 100 micrograms/ml) decreased f-MLP-induced chemotaxis and ionophore A23187-induced superoxide and LTB4 release in isolated neutrophils, and these effects were not blocked by the plasmin-inhibitor epsilon-aminocaproic acid (epsilon-ACA). On the other hand, plasmin (0.05 to 0.5 units/ml) also decreased these neutrophil functions but its effects were blocked in the presence of epsilon-ACA. Thus, while both t-PA and plasmin decrease neutrophil functions, effects of t-PA are independent of plasmin generation. Cumulative effects of t-PA and plasmin on neutrophil functions may relate to the overall efficacy of t-PA in thrombotic disorders.

Calcimycin↗
PubMed1989

Effects of peptide 6A on coronary blood flow dynamics in canine coronary thrombosis.

Intracoronary thrombi resulting in acute myocardial ischemia can often be lysed by thrombolytic agents. We examined the potential of a fibrin(ogen)-degradation product pentapeptide 6A (Ala-Arg-Pro-Ala-Lys), which increases coronary blood flow partly by stimulation of prostacyclin release, in reestablishing coronary blood flow in dogs with experimentally induced thrombus. An occlusive thrombus in the circumflex coronary artery was created by electrical stimulation of the endothelial surface. After the occlusive thrombus was stable without electrical current for at least 15 min, peptide 6A (5 mumol/min for 20 min intracoronary) or tissue-plasminogen activator (t-PA) [10 micrograms/kg/min for 20 min intravenously (i.v.)] was randomly administered. Peptide 6A administration reestablished coronary blood flow (peak 16 +/- 2 ml/min, mean +/- SE) in 6 of 12 animals with occlusive coronary thrombus. Mean time to blood flow reestablishment was 5.3 +/- 2.2 min, but the reflow was short lived (mean duration of reflow: 15.7 +/- 1.6 min). t-PA reestablished coronary blood flow (peak 19 +/- 3 ml/min) in 4 of 10 animals. The time of flow reestablishment was 12.0 +/- 3.9 min and the reflow persisted for 22.0 +/- 3.1 min. Peptide 6A administration was associated with an increase in coronary venous plasma 6-keto-PGF1 alpha, indicating stimulation of prostacyclin release. This study demonstrates the potential of peptide 6A in reestablishing coronary blood flow in a canine model of coronary thrombosis. This transient effect is associated with release of prostacyclin, which may be beneficial because of its vasodilator and platelet inhibitory effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A.

Previous studies demonstrate endothelium-dependent leukotriene D4 (LTD4)-induced relaxation of canine coronary arterial rings in vitro. We now show that coronary occlusion followed by reperfusion attenuates (P less than 0.01) the relaxation of canine coronary artery rings in response to LTD4 as well as acetylcholine (ACh), suggesting loss of endothelium-dependent coronary reactivity (n = 6 dogs). Since superoxide anions have been shown to cause breakdown of endothelium-derived relaxing factor (EDRF), we wondered whether treatment of dogs with superoxide anion scavenger superoxide dismutase (SOD) would modulate the effects of LTD4 and ACh on reperfused coronary artery rings. Indeed, treatment of dogs (n = 5) with SOD before coronary reperfusion resulted in preservation of LTD4- and ACh-induced relaxation of coronary rings. Treatment of another five dogs with selective thromboxane-synthetase blocker U 63557A before coronary reperfusion also resulted in preservation of coronary ring relaxation in response to LTD4 and ACh. To determine the mechanism of U 63557A-induced preservation of coronary reactivity, canine neutrophil superoxide anion generation in the presence of U 63557A was measured. Although U 63557A had no effect on superoxide anion generation in neutrophils alone, it markedly (P less than 0.02) inhibited superoxide anion generation in neutrophils in the presence of platelets, most likely via shunting of accumulated cyclic endoperoxide in platelets toward formation of prostacyclin, which inhibits neutrophil superoxide anion production. Thus SOD and U 63557A protect against loss of endothelium-mediated vascular relaxation by LTD4 and ACh after coronary occlusion and reperfusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Modulation of vascular tone by neutrophils: dependence on endothelial integrity.

To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)-10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Impaired canine coronary vasodilator response to acetylcholine and bradykinin after occlusion-reperfusion.

Previous studies indicate impairment of coronary arterial ring relaxation in response to acetylcholine (ACh) following coronary reperfusion, mediated via loss of endothelium-derived relaxing factor (EDRF). To examine if coronary vasodilator reserve is reduced following coronary occlusion-reperfusion in intact animals, 16 open-chest mongrel dogs were subjected to 1 hour of total left circumflex (Cx) coronary artery occlusion followed by reperfusion for 1 hour. Prior to Cx occlusion, coronary blood flow increased and vascular resistance decreased (both p less than or equal to 0.01) in response to ACh and bradykinin (BK). Following reperfusion, increase in Cx coronary flow in response to both vasodilators was significantly (p less than or equal to 0.01) impaired. Myocardial histology showed extensive neutrophil infiltration and capillary plugging by neutrophils in the Cx compared with the left anterior descending coronary artery-supplied myocardium. Myocardial myeloperoxidase activity was also increased in the Cx compared with the left anterior descending region (p less than or equal to 0.02). Pretreatment of four dogs with indomethacin partially reduced the vasodilator response to BK but not to ACh. However, indomethacin did not affect reperfusion-induced attenuation of BK or ACh's coronary vasodilator effects. To determine if calcium blocker verapamil would modify reperfusion-induced impairment in coronary vasodilator reserve, six dogs were treated with verapamil. Although verapamil enhanced coronary vasodilator effects of ACh and BK, it did not modify reperfusion-induced attenuation of coronary vasodilator reserve. Myocardial neutrophil accumulation and myeloperoxidase activity was also similar in control, indomethacin, and verapamil-treated dogs. These observations suggest that coronary reperfusion impairs coronary vasodilator reserve in intact dogs. This impairment is not modified by prostaglandin inhibition or by calcium blockade. Besides loss of EDRF, capillary plugging by neutrophils may contribute to the altered coronary flow reserve observed in the immediate post-reperfusion period. Furthermore, indomethacin or verapamil are not effective in modifying the reperfusion-related impairment of coronary vasodilator reserve.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Protection by superoxide dismutase from myocardial dysfunction and attenuation of vasodilator reserve after coronary occlusion and reperfusion in dog.

Previous studies indicate impairment of coronary arterial ring relaxation and loss of coronary vasodilator reserve after coronary artery occlusion and reperfusion. These changes are mediated in part through loss of endothelium-derived relaxing factor (EDRF) and/or myocardial neutrophil accumulation. To examine if superoxide dismutase (SOD), a scavenger of superoxide radicals, would modify the diminished coronary vasodilator reserve after temporary coronary occlusion in the intact animal, open-chest mongrel dogs were subjected to 1 hour of circumflex (Cx) coronary artery occlusion followed by 1 hour of reperfusion and treated with saline or SOD. Before Cx occlusion, coronary blood flow increased, and vascular resistance decreased (both p less than 0.01) in response to EDRF-dependent vasodilator acetylcholine as well as EDRF-independent vasodilator nitroglycerin. After Cx reperfusion, resting Cx coronary blood flow and vascular resistance were similar to the preocclusion values. In the saline-treated animals, there was evidence of myocardial dysfunction, which was measured by segmental shortening (-6 +/- 2% vs. 10 +/- 2%). Furthermore, increase in Cx coronary blood flow and reduction in vascular resistance in response to both vasodilators were significantly (p less than 0.01) impaired; these occurrences suggested loss of coronary vasodilator reserve. Myocardial histology showed extensive capillary plugging by neutrophils in the Cx-supplied myocardium. Myocardial myeloperoxidase activity, an index of neutrophil infiltration, was also increased in the Cx compared with the left anterior descending coronary artery region (p less than 0.02). Treatment of dogs with SOD, started at the end of Cx occlusion and continued during reperfusion, exerted significant (p less than 0.01) protective effect against reperfusion-induced attenuation of coronary vasodilator reserve in response to both acetylcholine and nitroglycerin. Loss of myocardial function (segmental shortening 5 +/- 1% vs. 10 +/- 1%) was less than in the saline-treated animals (p less than 0.01). Cx region-myocardial neutrophil accumulation and myeloperoxidase activity were also less (p less than 0.02) in the SOD-treated than in the saline-treated dogs. These observations suggest that coronary reperfusion impairs coronary vasodilator reserve in intact dogs. This impairment can be modified by treatment of animals with SOD before reperfusion. Capillary plugging by neutrophils may contribute to the altered coronary vasodilator reserve observed in the immediate postreperfusion period, and SOD modifies this reperfusion-induced impairment.

Acetylcholine↗
PubMed1989

Endothelium-dependent relaxation of rat aortic rings by leukotriene D4: importance of the magnitude of preload.

Leukotriene D4 (LTD4) generally constricts vascular smooth muscle resulting in reduction in blood flow in a variety of blood vessels which can be blocked by specific LT-receptor antagonists. LTD4 has also been shown to cause vasodilation in some animal species. To examine the basis of vasodilation, we evaluated the effects of LTD4 (10(-9) to 2 X 10(-6) M) on precontracted rat thoracic aortic rings in a tissue bath. LTD4 caused relaxation of the rat thoracic rings in a concentration-dependent fashion. This relaxant effect of LTD4 on rat aortic rings was observed regardless of the stimulus used for precontraction, such as l-epinephrine, l-norepinephrine, KCl, 5-hydroxy-tryptamine, or non-pharmacologic manual stretch. This relaxant effect of LTD4 was not blocked by inhibition of vascular eicosanoid synthesis with indomethacin or LT-receptor blockade with two different agents FPL-55712 or LY171883. However, de-endothelialization of rat thoracic aortic rings or treatment of aortic rings with the 5-lipoxygenase inhibitor nordihydroguaiaretic acid abolished the relaxant effect of LTD4. In addition, pretreatment of rings with an inhibitor of endothelium-derived relaxing factor (EDRF), free hemoglobin, also resulted in inhibition of LTD4-induced vascular relaxation. These observations suggest that the rat aortic ring relaxation by LTD4 is endothelium-dependent and is probably related to the release of EDRF.

Acetophenones↗
PubMed1988

Alterations in platelet alpha 2-adrenoceptors by aspirin.

Epinephrine-induced platelet aggregation (mediated through interaction with alpha 2-adrenoceptors) is inhibited by aspirin. To determine if aspirin modulates alpha 2-adrenoceptors, we quantitated dissociation constant (KD) and maximum number of binding sites (Bmax) on isolated platelet membranes using alpha 2-antagonist 3H-yohimbine in normal subjects given 650 mg of aspirin orally. Alpha 2-receptor KD increased from 3.20 +/- 1.80 to 7.32 +/- 3.32 nM (p less than 0.02) and Bmax from 115 +/- 77 to 190 +/- 140 fmol/mg protein. To determine if these alterations in alpha 2-receptors by aspirin were mediated through circulatory or intracellular effects, intact platelets or isolated platelet membranes were incubated with aspirin for 30 minutes in vitro. In these in vitro experiments, alpha 2-receptor KD increased from 2.92 +/- 1.76 to 9.83 +/- 8.55 nM and Bmax from 140 +/- 81 to 191 +/- 129 fmol/mg protein (p less than 0.05). Oral ingestion of aspirin or incubation of aspirin with intact platelets or lysates increased (3 to 10 fold) the concentration of 1-epinephrine required for inhibition of 3H-yohimbine binding by 50% (p less than 0.05). Basal platelet cyclic AMP as well as its elevation with PGE1 or PGI2 and decrease with catecholamines were not influenced by aspirin treatment of platelets. These data indicate that aspirin decreases platelet alpha 2-receptor affinity for agonist as well as antagonist. These effects of aspirin are independent of circulatory or dynamic intraplatelet changes.

Aspirin↗
PubMed1988

Dietary supplementation with omega-3 polyunsaturated fatty acids in patients with stable coronary heart disease. Effects on indices of platelet and neutrophil function and exercise performance.

It has been suggested that omega-3 polyunsaturated fatty acids (PUFAs) may alter the course of coronary artery disease by influencing platelet and neutrophil function, arachidonic acid metabolism, and circulating lipid concentrations. To examine this hypothesis, placebo or omega-3 PUFAs as Max-EPA (equivalent to 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid daily) was administered to eight patients with stable coronary artery disease and positive exercise stress test results in a randomized, double-blind, crossover fashion over a 12-week period. With Max-EPA administration, platelet aggregation threshold to epinephrine was increased in only two patients, but neutrophil aggregation and chemotaxic functions decreased consistently (both p less than or equal to 0.01 compared with preceding placebo phase) in all eight. Serum and platelet-rich plasma thromboxane B2 concentrations decreased 40 percent and 28 percent, respectively (both p less than or equal to 0.05). Neutrophil leukotriene B4 formation decreased 23 percent (p less than or equal to 0.01) and synthesis of leukotriene B5 became apparent in all subjects. Serum triglyceride concentrations fell 52 percent (p less than or equal to 0.05) without significant change in total cholesterol, high-density lipoprotein-cholesterol, or low-density lipoprotein-cholesterol concentrations. Systolic blood pressure and the double product (heart rate X systolic blood pressure) were lower (p less than or equal to 0.05) at the end of the Max-EPA phase than in the preceding placebo phase. Heart rate, systolic blood pressure, and the double product were also lower (p less than or equal to 0.05) at three as well as at six minutes of an exercise stress test, indicating a significant reduction in myocardial oxygen demand. Despite these alterations in platelet and neutrophil function, arachidonic acid metabolism, serum triglyceride concentrations, and myocardial oxygen demand, there were no significant changes in subjective parameters of coronary artery disease during the Max-EPA phase (angina frequency 3.7 versus 2.8 episodes per week, nitroglycerin consumption 3.0 versus 1.9 tablets per week, both p = NS). Similarly, exercise times to ST-segment depression (6.5 versus 4.1 minutes) and to onset of angina (5.4 versus 5.0 minutes) were not altered by administration of Max-EPA. Thus, short-term dietary supplementation with omega-3 PUFAs to patients with stable coronary artery disease does not appear to alter subjective or objective parameters of myocardial ischemia.

Aged↗