Thromboxane B2, 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 plasma levels in arteriosclerosis obliterans: relationship to clinical manifestations, risk factors, and arterial pathoanatomy

Current concepts of atherogenesis based on animal and human investigations indicate prostaglandins as a key factor in atherosclerotic lesions. The plasma profiles of thromboxane B2 (TXB2), 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 were investigated by means of a sensitive radioimmunoassay technique in 40 patients with arteriosclerosis obliterans and in 30 healthy control subjects. Abnormally high levels of TXB2 and PGE2 (222.97 +/- 320.86 pg/ml, mean +/- SD, vs 20 +/- 2.1 and 352.66 +/- 235.54 vs 24.4 +/- 3, p less than 0.01) were detected in arteriosclerosis obliterans patients. The ratio between TXB2 and 6-keto-PGF1 alpha was increased from 1.2 in control subjects to 6.0 in patients. In arteriosclerosis obliterans TXB2 increased in relation to clinical manifestations and to the extension of the vascular damage. In addition, TXB2 was positively related to serum triglyceride content (r = 0.562, p less than 0.05) and inversely related to platelet count (r = 0.727, p less than 0.001). The marked imbalance between the stable metabolites of thromboxane and prostacyclin in arteriosclerosis obliterans patients provides biologic evidence which fits well with the thrombogenic theory of atherosclerosis. These results further support the theory that prostaglandins may be heavily involved in atherosclerosis.     

Impaired cardiac PGI2 and PGE2 biosynthesis in patients with angina pectoris

Thirty-four patients with unstable angina and 14 patients with stable effort angina were investigated for cardiac prostacyclin and prostaglandin E2 (PGE2) biosynthesis, under resting conditions and after cold pressor testing. Twenty-seven patients undergoing cardiac catheterization and coronary angiography for congenital or acquired heart diseases other than coronary artery disease were studied as a control group. Prostacyclin (as 6-keto-PGF1 alpha) and PGE2 were measured by specific radioimmunoassay of blood from the coronary sinus and aorta. During resting conditions no significant differences in plasma 6-keto-PGF1 alpha and PGE2 concentrations were found between coronary sinus and aortic blood, and no transcardiac gradient existed either in control subjects or in patients with stable and unstable angina, respectively. In control subjects cold pressor testing induced a significant increase in 6-keto-PGF1 alpha and PGE2 levels in blood from the different sampling sites, and a significant transcardiac gradient occurred (+11.2 +/- 6.4 pg/ml for 6-keto-PGF1 alpha and +5.1 +/- 3.4 pg/ml for PGE2). However, in angina patients no significant increase in 6-keto-PGF1 alpha and PGE2 plasma levels was found and no transcardiac gradient was formed after cold pressor testing. These results indicate impaired cardiac prostacyclin and PGE2 biosynthesis both in patients with stable and unstable effort angina.     

Evaluation of plasma 6-keto-prostaglandin F1 alpha and thromboxane B2 in diabetic neuropathy

The relationship between diabetic neuropathy on the one hand and microangiopathy and arteriosclerosis on the other was studied by determining plasma 6-keto-prostaglandin F1 alpha (PGF1 alpha) and plasma thromboxane B2 (TXB2) in diabetics with neuropathy. The subjects were 13 patients with insulin independent diabetes mellitus with polyneuropathy (DN+ group), 9 cases which had no neuropathy (DN- group) and 6 control cases. The patients with severe retinopathy, nephropathy and hypertension were excluded. Plasma 6-keto-PGF1 alpha and plasma TXB2 concentration were determined by radioimmunoassay. The motor neuron conduction velocity (M.C.V.) was measured through the tibial nerve in all diabetics. Plasma 6-keto-PGF1 alpha was 116.3 +/- 4.2 pg/ml (mean +/- SE) in the DN+ group and 139.9 +/- 3.0 in the DN- group, each group showing a significant fall over the control with 150.8 +/- 4.5. Plasma 6-keto-PGF1 alpha in the DN+ group showed a significant decrease in comparison with that in the DN- group. As to plasma TXB2, there was no significant difference among the three groups. The M.C.V. fell off significantly in the DN+ group with 52.9 +/- 3.2 m/sec. Furthermore, a significant positive correlation was observed between M.C.V. and plasma 6-keto-PGF1 alpha. The following is the summary of these results. A decrease in plasma 6-keto-PGF1 alpha was observed in diabetics with polyneuropathy. A decrease in the production of prostacyclin (PGI2) due to impairment of vascular endothelium in the nerve tissue was surmised. The decrease in plasma 6-keto-PGF1 alpha presumably stimulates the activity of platelet agglutination and causes an ischemic change in the nerve tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous biosynthesis of prostacyclin during cardiac catheterization and angiography in man

The potent platelet inhibitory and vasodilator properties of prostacyclin suggest that levels of this substance may be of relevance to drug action and pathologic processes in the coronary vascular bed. Attempts to estimate the coronary secretion rate of prostacyclin have relied on measurements of metabolites obtained via cardiac catheter, usually as an adjunct to coronary angiography. To test the hypothesis that such procedures might themselves perturb endogenous biosynthesis of prostacyclin we used mass spectrometry to measure plasma levels of 6-keto-prostaglandin (PG) F1 alpha across the coronary vascular bed, as well as to assess the excretion of a major urinary metabolite, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), in patients undergoing cardiac catheterization. PGI-M excretion increased variably from a median 100 to 205 pg/mg creatinine (p less than .01) during catheterization with angiography and remained elevated 2 to 4 hr after initiation of the procedure. However, cardiac catheterization without angiography also stimulated metabolite excretion, perhaps reflecting catheter-induced vascular trauma. The direct effect of radiocontrast media on vascular release of prostacyclin was indicated by increased PGI-M excretion in healthy volunteers administered intravenous radiocontrast and by studies of the canine coronary artery and jugular vein in vitro. Measurement of plasma 6-keto-PGF1 alpha after left heart catheterization showed that levels in aortic (21 +/- 8 pg/ml) and coronary sinus (14 +/- 2 pg/ml) blood were increased compared with peripheral venous levels (less than or equal to 4 + 1 pg/ml) determined before this procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet activation during thrombolysis and percutaneous transluminal coronary angioplasty in the acute phase of myocardial infarction

To clarify the mechanism of recanalization and reocclusion in thrombolysis and percutaneous transluminal coronary angioplasty (PTCA), the plasma concentrations of beta-thromboglobulin (beta-TG), thromboxane B2 (TXB2) and platelet aggregation adenosine diphosphate (ADP) (2 microM/ml, collagen 2 micrograms/ml) were assessed in 11 normal subjects and in 19 patients with acute myocardial infarction whose infarct-related vessels were recanalized by thrombolysis and/or PTCA. In patients with acute myocardial infarction, the plasma concentrations of beta-TG and TXB2 were significantly higher than those in normal subjects (beta-TG: 128 +/- 132 ng/ml vs 38 +/- 17 ng/ml, TXB2: 131 +/- 154 pg/ml vs 36 +/- 18 pg/ml). Collagen-induced platelet aggregation decreased significantly in patients with acute myocardial infarction; whereas, ADP-induced platelet aggregation showed no significant difference. Infarct-related vessels recanalized by thrombolysis (seven patients: group 1) and PTCA (seven patients: group 2) were patent on the follow-up angiograms. Infarct-related vessels were reoccluded in five patients immediately after PTCA or during the follow-up angiography (group 3). Beta-TG and TXB2 did not change before and after recanalization in groups 1 and 2, but increased significantly after recanalization in group 3 (beta-TG: 155 +/- 185 ng/ml----269 +/- 233 ng/ml, TXB2: 104 +/- 87 pg/ml----169 +/- 91 pg/ml). Platelet aggregation did not differ significantly among the three groups. We concluded that platelets are not activated during thrombolysis and/or PTCA in cases without reocclusion, while platelets are markedly activated during PTCA in cases with reocclusion. Thus, it is suggested that platelet activation plays an important role in the mechanism of reocclusion.     

Proinflammatory cytokines (IL-6, TNF-alpha) and cardiac troponin I (cTnI) in serum of young people with ventricular arrhythmias

In the most cases the origin of ventricular arrhythmias is ischaemic, necrosis focus or presence of the connective tissue in cardiac muscle. The aim of the study was to evaluate troponin I (cTnI), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) vs in young subject with ventricular arrhythmias. Into the study group included young people without organic heart diseases, dyselectrolitemia, with normal ECG which has not elevated levels of C-reactive protein (55 persons). The control group consisted of 22 healthy persons. The values of cTnI were not increased. The TNF-alpha concentrations were elevated in persons with ventricular arrhythmias (92 +/- 232 pg/mL vs. 2 +/- 1 pg/mL, p < 0.001). The IL-6 concentrations were slightly elevated without statistical significance (1.5 +/- 4.5 pg/mL i 0.1 +/- 0.04 pg/mL, p = 0.06). CONCLUSIONS: There was no evidence of myocardial injury in young people with ventricular arrhythmias (cTnI). We noted increase levels of proinflammatory cytokines. It might suggest that the background of ventricular arrhythmias is inflammation.     

Sudden death induced by intracoronary platelet aggregation

Sodium arachidonate (AA, 1.5 mg/kg) was injected into the coronary arteries in 16 rabbits. Arrhythmia, marked ST-T depression and apnea appeared in all cases, and 7 cases died within 10 min after the AA. Before the injection, the thromboxane B2 (TXB2) value was 1.2 +/- 0.2 ng/ml (mean +/- SE) and the 6-keto-PGF1 alpha value was 2.1 +/- 0.4 ng/ml. Three minutes after the AA, TXB2 values were 5.0 +/- 1.1 in the surviving cases and 17.9 +/- 6.5 ng/ml in the cases which died. 6-keto-PGF1 alpha values were 47.7 +/- 4.6 in the surviving cases and 248.5 +/- 69.3 ng/ml in the cases which died. There occurred no deaths in 7 cases pretreated with aspirin (ASA) and in 11 cases pretreated with OKY-046 and 1581, which are specific inhibitors of TXA2 synthetase. TXB2 values did not change in the ASA and OKY groups after the AA injection. 6-keto-PGF1 alpha values did not change in the ASA group and increased in the OKY group after the AA injection. Histological findings of the heart showed more remarkable ischemic changes in the non-pretreated group than in the ASA and OKY groups. These results suggest a role for TXA2 in sudden death. PGI2 production was extremely enhanced, suggesting the presence of a protective mechanism against thrombogenesis in vivo.     

Abnormal cardiocoronary thromboxane A2 production in patients with unstable angina

Thromboxane B2 (TXB2), the stable metabolite of thromboxane A2 (TXA2), was measured in the coronary sinus and in aortic blood before and after cold pressor test (CPT) in 21 patients suffering from ischemic heart disease (7 affected by stable effort angina and 14 by unstable angina) and in 12 patients not suffering from myocardial ischemia (control group) during coronary angiography. Aspirin (10 mg/kg intravenously) was administered before catheterization in order to prevent platelet and leukocyte TXA2 formation. Control subjects and patients with effort angina had TXB2 resting levels lower than unstable angina patients without a transcardiac gradient which, on the contrary, was found in unstable angina patients. Only in these patients CPT resulted in a significant TXB2 increase more marked in the coronary sinus (from 50.0 +/- 18.9 pg/ml to 73.0 +/- 35.1 pg/ml, p less than 0.001) than in the aorta (from 33.4 +/- 17.1 pg/ml to 42.6 +/- 24.0 pg/ml, p less than 0.05), so that the transcardiac TXB2 gradient significantly increased. In all but two unstable angina patients, TXB2 elevation was not associated with a fall of cardiac lactate extraction. The resting and CPT-induced TXB2 gradients were unrelated to the presence and severity of coronary angiographic lesions. These results indicate that unstable angina patients show an abnormal cardiocoronary capacity to synthesize TXA2, which seems not to be elicited by the occurrence of myocardial ischemia.     

Effect of aging on 6-keto-PGF1 alpha levels in normotensive and essential hypertensive males

Prostacyclin (PGI2) is produced in the vessel wall and acts as a vasodilator hormone. Measurement of plasma 6-keto-PGF1 alpha is considered to be an index of PGI2 production. In the present study the effects of aging on the plasma 6-keto-PGF1 alpha levels were studied in 64 normotensive and 48 essential hypertensive males. The subjects were divided into 3 groups, i.e., young (24-39 years), middle-aged (40-55 years) and elderly (over 56 years) groups. Plasma 6-keto-PGF1 alpha was measured by specific radioimmunoassay after silicic acid column chromatographic purification. The 6-keto-PGF1 alpha levels were lower in elderly normotensive males (10.3 +/- 1.4 pg/ml, mean +/- SE, n = 12) than in normotensive young males (15.3 +/- 2.3, n = 30, p less than 0.05). The plasma 6-keto-PGF1 alpha levels in hypertensive elderly males (10.6 +/- 1.3 pg/ml, n = 10) is lower than in hypertensive young males (19.8 +/- 2.2, n = 17, p less than 0.01). These results indicate that the plasma 6-keto-PGF1 alpha levels decreased with age in both normotensive and hypertensive groups. Thus, PGI2 production may decrease with age.     

Role of prostaglandins, histamine, and serotonin in the pathophysiology induced by Pasteurella hemolytica endotoxin in sheep

Pasteurella hemolytica endotoxin (12 micrograms/kg) was infused intravenously into ewes over 500 min. Blood was sampled for 60 min before the infusion and at intervals during the infusion and for 1500 min postinfusion. The control values for plasma TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin were 283 +/- 53 pg/ml (mean +/- standard error of mean), 281 +/- 14 pg/ml, 199 +/- 27 pg/ml, and 56.8 +/- 2.0 ng/ml, respectively. The plasma concentrations of TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin significantly increased to a maximum at 50 min of infusion to 359%, 344%, 313%, and 201% of the control, respectively. PGF2 alpha and TxB2 returned to control levels at 300 min during infusion and 6-keto-PGF1 alpha at 60 min postinfusion and serotonin at 100 min of infusion. Serotonin concentration decreased significantly at 450 min of infusion to 73% of control and returned to control level at 1500 min postinfusion. No significant changes were found in the plasma levels of PGE, histamine, and ACE activity. We conclude that release of TxA2, PGI2, PGF2 alpha, and serotonin may contribute to pathophysiology induced by P. hemolytica endotoxin in sheep.     

Studies on the interrelation of plasma 6-keto-prostaglandin F1 alpha, thromboxane B2 and diabetic microangiopathy

Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TXB2) were measured in 55 diabetics and 30 controls with radioimmunoassay. The correlation between diabetic microangiopathy and the ratio of TXB2 and 6-keto-PGF1 alpha was analysed. Diabetics were divided into three groups according to the change of retina and renal function. Group A, diabetics without microangiopathy; group B, diabetics with slight microangiopathy; and group C, diabetics with severe microangiopathy. The results showed that the ratio of TXB2/6-keto-PGF1 alpha was higher in B and C groups (0.997 +/- 0.31 1.10 +/- 0.25 means +/- S) than in the controls (0.72 +/- 0.17 means +/- S) (P less than 0.01). Group A patients had slightly higher level of the ratio (0.85 +/- 0.20 means +/- S) than the controls but the difference was not significant. The results suggest that the TXB2 and 6-keto-PGF1 alpha imbalance exists only in diabetics with microangiopathy and their imbalance might have more significance in the pathogenesis of diabetic microangiopathy than their individual change.     

Correlation of flow mediated dilation with inflammatory markers in patients with impaired cardiac function. Beneficial effects of inhibition of ACE

Impaired cardiac function is frequently accompanied by peripheral vascular dysfunction and a pro-inflammatory condition, which may be associated with elevated levels of angiotensin II. We hypothesized that the magnitude of flow mediated dilatation (FMD) of the brachial artery of post myocardial infarction patients will correlate with serum levels of tumor necrosis factor alpha (TNFalpha) and C-reactive protein (CRP), and that treatment with angiotensin converting enzyme inhibitors (ACEI) will increase FMD by reducing TNFalpha and CRP. Patients were treated with low dose (10 mg/day) quinapril (Q) or enalapril (E) and their effects on FMD and inflammatory markers were evaluated after 8 and 12 weeks. Before treatment, in both groups FMD showed a low value (Q: 2.95+0.42% and E: 3.3+/-0.33%), whereas TNF-alpha (Q: 31.65+/-8.23 pg/ml and E: 29.5+/-5.9 pg/ml) and CRP (Q: 7.28+/-2.96 mg/ml and E: 7.08+/-3.02 mg/ml) were elevated. In the Q group, but not in the E group FMD increased significantly, (to 5.96+1.10%), whereas TNF-alpha (19.0+/-12.21 pg/ml) and CRP (to 3.91+/-1.82 mg/L) significantly decreased after 8 and 12 weeks of Q treatment. Moreover, the magnitude of FMD showed a strong inverse correlation with serum levels of TNF-alpha and CRP after Q treatment. Thus, in post myocardial infarction patients endothelial dysfunction assessed by FMD correlates with elevated levels of plasma inflammatory markers, and low dose quinapril improves endothelial function, likely by reducing vascular inflammation.     

D-Arg-[Hyp3-D-Phe7]-bradykinin, a bradykinin antagonist, reduces mortality in a rat model of endotoxic shock

The kallikrein-kinin system is activated during endotoxic shock, suggesting that bradykinin plays a role in the pathology of this disease. To test this hypothesis, a bradykinin antagonist, D-Arg-Hyp3-D-Phe7-bradykinin (NPC 567), was studied in conscious, chronically catheterized rats undergoing lipopolysaccharide (LPS)-induced endotoxic shock. LPS treatment resulted in an increase in circulating bradykinin from less than 23 pg/ml to 144 +/- 18 pg/ml at 1 hr. Intravenous administration of LPS resulted in a 38% drop in mean arterial pressure at 1 hr which was partially reversed by NPC 567. NPC 567 did not affect the moderate tachycardia observed following LPS. NPC 567 infusion at 8 nmol/kg/min dramatically reduced mortality from 100% to 50% at 24 hr (P less than 0.01). In response to LPS, blood thromboxane B2 (TXB2) rose from less than 200 pg/ml to 2,298 +/- 64 pg/ml, while 6-keto-prostaglandin-F1 alpha (6kPGF1 alpha) rose from 289 +/- 23 pg/ml to 7,927 +/- 822 pg/ml. NPC 567 reduced the rise in 6kPGF1 alpha by 42% (P less than 0.05), without affecting TXB2. In summary, NPC 567 reduced mortality in rats treated with LPS, reduced the rise in 6kPGF1 alpha and partially reversed the hypotensive effects. These results suggest that bradykinin plays a significant role in the pathology of endotoxic shock.     

根治幽门螺杆菌三联疗法对冠心病患者内皮功能的影响

目的：根治探讨幽门螺杆菌（Hp）三联疗法对冠状动脉粥样硬化性心脏病（CHD）患者血管内皮功能的影响。方法纳入2010年10月～2013年2月大庆龙南医院院心内科住院14C尿素呼气试验（14C-UBT）阳性的冠心病患者104例,在常规治疗的基础上,进行根治Hp三联治疗（阿莫西林＋克拉霉素＋兰索拉唑）,疗程为7天,研究期为6个月。研究对象在试验前后检测血脂、血栓素B2（TXB2）和6-酮前列腺素F1α（6-keto-PGF1α）,并通过肱动脉内径变化S1进行内皮依赖性血管舒张功能（FMD）检测。结果治疗后患者的血浆总胆固醇（TC）、TXB2水平比治疗前明显降低[TC：（4.98±1.20） mmol/L vs.（5.43±1.87）mmol/L;TXB2：（240±41）pg/ml vs.（282±66）pg/ml],6-keto-PGF1α、CI明显升高[6-keto-PGF1α：（299±69）pg/ml vs.（217±64）pg/ml;S1：（7.86±0.39）% vs.（4.87±0.26）%）],差异有统计学意义（P＜0.05）。结论根治Hp三联疗法可改善合并Hp感染的冠心病患者血管内皮功能。     

Tumor necrosis factor (cachectin) in human visceral leishmaniasis

High tumor necrosis factor-alpha (TNF alpha) levels were present in the serum of 24 of 28 active visceral leishmaniasis (VL) patients (142.9 +/- 113.9 pg/ml, mean +/- SD), whereas levels were not elevated in 26 of 30 patients with cryptic leishmanial infection (16 asymptomatic, 4 with self-healing subclinical infection, and 10 posttreatment VL cases). Serum TNF alpha levels were also not elevated in 15 normal volunteers (11.3 +/- 15.6 pg/ml) and in 10 patients with tegumentary leishmaniasis (19.1 +/- 10.8 pg/ml). Leishmanial infection of human monocyte-derived macrophages enhanced the basal TNF alpha production by these cells, and this effect was further potentiated by treatment with recombinant interferon-gamma. After effective treatment of VL patients, serum TNF alpha levels dropped rapidly (129 +/- 112 vs. 9 +/- 13 pg/ml in 10 days), even before clinical parameters such as spleen size or parasitism, white blood cell count, or levels of hemoglobin returned to normal values. On the other hand, patients unresponsive to treatment remained with elevated levels (276 +/- 69 vs. 155 +/- 71 pg/ml in 10 days). Thus, serum TNF alpha levels in VL patients are a good parameter to monitor in determining host response to therapy.     

A study of the role of plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha in epidemic hemorrhagic fever

Plasma concentrations of Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were dynamically measured with radioimmunoassay in 30 patients of epidemic hemorrhagic fever (EHF). It was found that the levels plasma TXB2 significantly increased and 6-keto-PGF1 alpha decreased in EHF patients as compared with those in controls. The more severe the patient's condition, the higher the level of TXB2 and the lower the level of 6-keto-PGF1 alpha. The ratio of TXB2/6-keto-PGF1 alpha was parallel with the severity of the patient's condition. Plasma TXB and TXB2/6-keto-PGF1 alpha ratio increased significantly in the hemorrhagic and shock group, while 6-keto-PGF1 alpha decreased significantly in the shock group. The results showed that there is a distinct imbalance of TXA2-PGI2 mediated through the increase of TXA2 and decrease of PGI2 in EHF. The imbalance of TXA2-PGI2 participates in the pathogenesis and pathophysiology of hemorrhage, shock and renal dysfunction.     

Plasma and pericardial fluid natriuretic peptide levels in postinfarction ventricular dysfunction

AIMS: In the present study we examined plasma and pericardial fluid ANP and BNP concentrations in postinfarction ventricular dysfunction. The association of peptide levels to left ventricular (LV) dysfunction and to the localization of the myocardial infarction (MI) was studied. METHODS AND RESULTS: Plasma and pericardial fluid samples were obtained from 37 patients undergoing coronary bypass surgery. According to the ECG and preceding coronary angiography, the patients were divided into three groups: previous anterior myocardial infarction (MI) (n=12), previous inferior/posterior MI (n=15) and no history of MI (n=10). When compared to the control group with no MI, the patients with anterior MI had elevated plasma ANP and BNP (134+/-13 vs. 81+/-15 pg/ml, P<0.01 and 95+/-10 pg/ml vs. 26+/-8 pg/ml, P<0.01, respectively) and pericardial fluid BNP (473+/-60 pg/ml vs. 57+/-8 pg/ml, P<0.001) levels. The plasma natriuretic peptide concentrations were not increased in the patients with inferior/posterior MI, but the pericardial fluid BNP concentrations were greater than in the patients with no history of MI (129+/-35 pg/ml vs. 57+/-8 pg/ml, P<0.05). Six of the 12 patients with previous anterior MI had LVEF> or =45%. Despite their normal LV systolic function, these patients had increased plasma and pericardial fluid BNP levels when compared to the group with no history of MI (68+/-18 pg/ml vs. 26+/-8 pg/ml, P<0.05 and 534+/-258 pg/ml vs. 57+/-8 pg/ml, P<0.01, respectively). CONCLUSIONS: Previous anterior myocardial infarction was associated with increased cardiac BNP production even if the LV systolic function was normal (LVEF> or =45%). The high pericardial fluid BNP concentrations in postinfarction patients suggest that the BNP synthesis and release are augmented in the ventricular myocardium independent from the LVEF.     

Caffeine as a possible cause of ventricular arrhythmias during the healing phase of acute myocardial infarction

Caffeine (300 mg) was administered to each of 70 patients a mean (+/- standard error of the mean) of 7 +/- 1 days after the onset of acute myocardial infarction to determine its effects on ventricular arrhythmias. The study was designed as a randomized, double-blind, within-patient comparison between caffeine and placebo. Continuous Holter electrocardiographic recording for 4 hours showed no significant differences in the proportion of patients who had ventricular ectopic activity or the total number and complexity of ventricular premature complexes after caffeine vs placebo. Caffeine increased mean blood pressure from 116 +/- 2/70 +/- 1 mm Hg to a maximum of 125 +/- 3/78 +/- 2 mm Hg (p less than 0.001) at 4 hours. Plasma epinephrine increased (p less than 0.01) from 58 +/- 4 pg/ml to a maximum 88 +/- 6 pg/ml 3 hours after caffeine ingestion, whereas the plasma norepinephrine level did not change. Although caffeine caused significant hemodynamic and humoral responses in this population of relatively caffeine-naive postinfarction patients, it did not increase the occurrence or severity of ventricular arrhythmias.     

Evaluation of thromboxane production and complement activation during myocardial ischemia in patients with angina pectoris

BACKGROUND. The complement system and arachidonic acid metabolites are involved in severe myocardial ischemia such as myocardial infarction. Furthermore, there is experimental evidence for C5a participation in thromboxane production. METHODS AND RESULTS. We examined whether C5a and thromboxane are produced during brief and reversible episodes of myocardial ischemia induced in patients with stable angina. Twenty-five patients underwent either atrial pacing or percutaneous transluminal coronary angioplasty associated with arterial and coronary sinus blood sampling. Rapid atrial stimulation of patients with effort angina caused significant ST segment depression (delta ST = -1.7 +/- 0.2 mm), decreased fractional lactate extraction (from +12.8 +/- 2.5% baseline to -13.7 +/- 4.6% at peak ischemia, n = 13, p less than 0.001), and increased coronary sinus plasma thromboxane B2 levels (from 345 +/- 85 pg/ml baseline to 1,684 +/- 64 pg/ml at peak ischemia, p less than 0.01). Changes of fractional lactate extraction correlated significantly with changes of coronary sinus plasma levels of thromboxane B2. There was no change of coronary sinus 6-keto-PGF1 alpha levels. Similar pacing of control subjects (n = 6) did not cause release of lactate or thromboxane. Seventeen other patients underwent exercise testing with noninvasive measurements of thromboxane and prostacyclin metabolites in urinary samples collected before and after the test. No detectable increase of urinary 11-dehydrothromboxane B2 was measured in patients with stable angina after exercise-induced myocardial ischemia. However, basal 11-dehydrothromboxane B2 levels were significantly higher in patients with angina (105 +/- 25 pg/mmol creatinine, n = 9) than in control patients (45 +/- 8 pg/mmol creatinine, n = 8, p less than 0.05 between groups). Coronary sinus plasma levels of the anaphylatoxin C5a always remained below 4 ng/ml in patients undergoing pacing. More severe myocardial ischemia after coronary angioplasty (percent lactate extraction decreased from +24.8 +/- 2.7% baseline to -41.6 +/- 22.4% at peak ischemia, p less than 0.05) was not associated with C3a or C5b-9 generation. In all patients, there was neither platelet sequestration nor platelet alpha-granule release (no changes of beta-thromboglobulin/platelet factor 4 levels) into the coronary sinus plasma. CONCLUSIONS. Patients with stable angina have chronically increased thromboxane synthesis as assessed by excretion of urinary metabolites. Thromboxane is acutely released into the coronary sinus during pacing-induced ischemia without significant intracoronary platelet aggregation. Complement does not appear to be activated in stable angina during brief and reversible episodes of myocardial ischemia and does not contribute to thromboxane production.     

Plasma elevations of histamine and a prostaglandin metabolite in acute bronchiolitis

Acute bronchiolitis (AB) is a common lung disease in infants manifested clinically by dyspnea and wheezing. The purpose of this study was to measure simultaneous plasma levels of histamine and a stable prostaglandin F2 alpha metabolite [13,14-dihydro-15-keto-PGF2 alpha (PG metabolite)], by radioenzymatic and radioimmunoassays, respectively, during and after recovery from AB. Blood was obtained from 15 infants during AB and from 14 and 9 of these infants when re-evaluated 6 and 18 months later, respectively. Mean (+/- 1 SEM) pre- and posttherapy (inhaled isoetharine) histamine levels (pg/ml), 1,923 +/- 980 and 1,035 +/- 250 during AB, respectively, were markedly higher than those of the same nonwheezing subjects at 18 months, 360 +/- 125, but unexpectedly lower than those at 6 months, 9,210 +/- 5,242. Of the 14 infants evaluated at 6 months, 7 had elevated histamine levels along with histories of recurrent wheezing after AB. Similarly, pre- and posttherapy PG metabolite levels (pg/ml), 1,033 +/- 419 and 1,613 +/- 527, respectively, were significantly higher than those of the same children when asymptomatic at 6 (27 +/- 7) and 18 months (68 +/- 25). Pre- and posttherapy levels of histamine and PG metabolite were higher than those of normal and sick, nonwheezing infants. These data indicate that histamine and PG metabolite are detectable in plasma during AB and suggest a role for histamine and PGF2 alpha in the pathogenesis of airways inflammation in AB.