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The clinical and echocardiographic features of a case of endocarditis due to Actinobacillus actinomycetemcomitans uniquely involving the native tricuspid valve are presented. The importance of two-dimensional echocardiographic studies in the evaluation of patients with suspected endocarditis is emphasized.

Endogenous modulators of platelet aggregability and vascular tone may play a part in coronary-artery disease. We therefore measured the release of prostaglandins and thromboxane into the coronary circulation in patients with various kinds of cardiac disease. Simultaneous coronary-sinus (CS) and ascending-aortic (AO) blood samples were obtained from 60 patients for measurement of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, a prostaglandin I2 metabolite) and of thromboxane B2 (TxB2). Samples from 45 of these patients were also tested for prostaglandin E2 (PGE2) and lactate. Patients with unstable angina pectoris who reported chest pain within 24 hours of study had higher TxB2 CS/AO ratios (5.8 +/- 2.8, mean +/- S.D.) than patients whose most recent anginal pain was more than 96 hours before study (1.3 +/- 0.6; P less than 0.05), than those with nonischemic chest pain (1.2 +/- 0.4; P less than 0.05), or with valvular or congenital nonischemic heart disease (1.2 +/- 0.6; P less than 0.05). Those whose most recent anginal pain occurred 24 to 96 hours before study were distributed bimodally: the majority had low TxB2 CS/AO ratios (range, 0.5 to 2.1) like the patients in the three aforementioned groups, whereas a few had markedly elevated values (range, 10.5 to 46.6). The 6-keto-PGF1 alpha and PGE2 CS/AO ratios and myocardial lactate extraction were not significantly different among the five groups. These data suggest that local thromboxane release is associated with recent episodes of angina in patients with unstable angina pectoris, but whether this release is a cause or an effect is not yet known.

There is an abundance of information suggesting that prostaglandins are involved in the development and clinical expression of atherosclerosis. Many studies demonstrate a relationship between prostaglandins and the risk factors for peripheral and coronary artery disease. Thus, part of the mechanism by which hyperlipidemia, diabetes mellitus, smoking, hypertension, sex hormones, age, heredity, emotional stress and diet contribute to the development and progression of atherosclerosis may be through an imbalance between thromboxane A2 and prostaglandin I2. Recent studies show a temporal relationship between acute ischemic events (specifically, unstable angina) and a transcardiac increase in thromboxane B2, while others demonstrate a salutary effect of disaggregatory and vasodilatory prostaglandins in such patients. If prostaglandins and thromboxane prove important in ischemic vascular disease, attention will be directed at the correction of their pathologic imbalance. This may be accomplished by dietary manipulation as well as by the development of prostaglandin receptor antagonists or inhibitors of specific prostaglandin pathways.

Thromboxane A2 may play a role in coronary arterial spasm, unstable angina, myocardial infarction, cardiac arrhythmias, and sudden death. Although previous studies have examined peripheral, aortic, and coronary sinus concentrations of its stable metabolite, thromboxane B2 (TxB2), it is unknown, first, if blood sampling through long catheters alters the concentration of TxB2 and second, if peripheral levels of this prostanoid reflect its intracoronary production and release. In order to answer these questions, paired blood samples were obtained through an 18-gauge needle and a No. 7 or 8 French 110 to 125 cm catheter from the arterial (14 patients) and venous (16 patients) circulations; in addition, coronary sinus and peripheral venous samples were obtained in 16 patients and aortic samples were obtained in 14 of these patients. All samples were analyzed to TxB2 by radioimmunoassay. Blood sampling through long catheters did not systematically alter the concentrations of arterial TxB2 (needle, 85.5 +/- 67.5 pg/ml [mean +/- SD]; catheter, 62.3 +/- 40.9 pg/ml; p = 0.20) or venous TxB2 (needle, 182.5 +/- 170.5 pg/ml; catheter, 521.4 +/- 1536.0 pg/ml; p = 0.39). Peripheral venous TxB2 levels did not correlate with TxB2 levels in coronary sinus (r = 0.01) or the TxB2 coronary sinus/aortic ratios (r = 0.21). Thus blood sampling through long catheters across the coronary bed is both a reliable and necessary method for assessing intracoronary TxB2 production in patients with ischemic heart disease.

Endothelium of cerebral surface vessels (pial arterioles and venules) was injured with a light/dye technique in anesthetized mice. This induced platelet aggregation at the site of injury. The onset of aggregation was monitored through a microscope in mice given angiotensin II acetate, 4 micrograms i.v. 30 minutes earlier. Aggregation latency was compared with that in vehicle treated (saline) mice. Angiotensin II caused a highly significant delay in aggregation within the arterioles which was not related to a change in shear rate of blood. Angiotensin II added to platelet rich plasma, failed to influence the aggregation produced by subsequent addition of 0.5 microM ADP or 0.5 mM sodium arachidonate. Angiotensin is a well known stimulator of prostacyclin synthesis or release, and angiotensin has been reported to inhibit platelet aggregation ex vivo by increasing prostacyclin in the effluent superfusing the mass of aggregating platelets. Our data represent the first report of an antiaggregating effect of angiotensin II in vivo in an intact microvascular bed. The data is consonant with the literature describing increased prostacyclin levels following angiotensin II infusion. The antiaggregating effect of angiotensin in cerebral microvessels may help explain a recent observation describing increased survival of gerbils treated with angiotensin following carotid ligation.

We investigated the relationship between glucose levels and platelet thromboxane production or aortic prostacyclin production, using radioimmunoassay (RIA) to measure thromboxane B2 and 6-keto-PGF1 alpha. We found a direct relationship (p less than .05) between plasma glucose levels and thromboxane A2 production by arachidonate stimulated platelets in platelet rich plasma of normal mice. However, when mice were deprived of food overnight, the glucose level fell but the TxB2 production rose significantly. Moreover, mice with streptozotocin diabetes had significantly elevated glucose levels, but normal TxB2 production, which also rose significantly after fasting. Thus in our laboratory both fasting and diabetes nullify or reverse the direct relationship between glucose levels and TxB2 production seen in normal fed mice. This makes it difficult to ascribe the correlation between glucose and TxB2 levels in normal fed animals to cause and effect. RIA revealed an inverse correlation between glucose levels and 6-keto-PGF1 alpha production which was highly significant in aortas taken from fasted mice and stimulated for 10 minutes with 0.1 mM arachidonate. This inverse correlation was present with either normal or diabetic aortas. Moreover, fasting increased the production of 6-keto-PGF1 alpha. However there was a significant elevation of 6-keto production by aortas of mice with diabetes of 5-6 weeks duration, compared to aortas of normal mice. Therefore either diabetes in these mice reversed a normal inhibitory effect of glucose on 6-keto production, or else the inverse correlation between glucose levels and 6-keto production does not represent a cause and effect relationship between the two variables.

Thromboxane A2 exerts powerful effects on vascular smooth muscle tone and platelet aggregability. Previous studies have demonstrated increases in transcardiac thromboxane B2 (a stable thromboxane A2 metabolite) in patients with unstable angina and recent chest pain. To determine whether these increases in transcardiac thromboxane B2 are unique to the unstable anginal syndrome or are merely a consequence of ongoing myocardial ischemia, simultaneous ascending aortic and coronary sinus blood samples were obtained for quantitation of thromboxane B2 in 52 patients with a history of chest pain. Provocation was performed with (1) rapid cardiac pacing in 23 patients, (2) cold pressor stress in 19 patients, and (3) sustained isometric exertion in 10 patients. Of the 52 patients, only 5 had a substantial (greater than 3-fold) increase in coronary sinus thromboxane B2 in response to provocation: 1 had unstable angina and chest pain during the previous 48 hours and 4 had a myocardial infarction within the previous 6 weeks. Similarly, only 7 had a greater than 3-fold increase in the coronary sinus/aortic thromboxane B2 ratio in response to provocation: 1 had unstable angina and recent chest pain, 5 had a recent myocardial infarction, and 1 had both of these. There were no other clinical features unique to these patients. The remaining patients with similar diagnoses did not develop a marked increase in coronary sinus thromboxane B2 or the coronary sinus/aortic thromboxane B2 ratio with provocation. None of the 35 patients with stable ischemic heart disease or nonischemic chest pain syndromes had a substantial increase in coronary sinus thromboxane B2 or the coronary sinus/aortic thromboxane B2 ratio (p less than 0.001 for both coronary sinus thromboxane B2 and the coronary sinus/aortic thromboxane B2 ratio in comparison with the 17 patients with recent unstable angina or myocardial infarction). Thus, generous amounts of thromboxane B2 are released into the coronary circulation after provocation in some patients with unstable angina or recent myocardial infarction but not in those with stable ischemic heart disease or nonischemic chest pain syndromes.

To assess the contribution of cardiac innervation toward understanding the mechanisms of bradycardia during contrast coronary angiography, heart rate (HR) responses in eight patients after heart transplantation were compared with 10 normal patients (control), 10 patients with coronary artery disease (CAD) and normal ventricular function, and 10 patients with congestive cardiomyopathy and normal coronary arteries. The longest P-P interval was measured beat to beat before (HR 1) and after (HR 2) coronary angiography. The coronary vessel perfusing the sinus node did not influence HR 2 responses within each group. HR 1 was significantly different from HR 2 (p less than 0.05) in the control and CAD groups but was not different in the transplant and cardiomyopathy groups. Compared with the control group, the percent decrease in HR was significantly less in transplant patients than in patients with cardiomyopathy. Thus contrast injection bradycardia is absent in denervated patients after heart transplant, and this response is markedly blunted in cardiomyopathy patients who are known to have diminished vasodepressor reflexes. These findings suggest that the bradycardia response is probably a neurally mediated phenomenon.

The effects of ibuprofen (I) were studied in the Pseudomonas (P) porcine ARDS model. Pigs, 14-26 kg (5 in each group), were anesthetized and ventilated with 0.5 FiO2 and 5 cm H2O PEEP. A control (C) group received saline only, a second group was given P, 1 X 10(8) org/ml at 0.3 cc/20 kg/min, and a third group was given P followed by 12.5 mg I at 20 and 120 min. Pulmonary arterial (PAP), wedge (PWP) and systemic arterial pressures, cardiac output (CO), and thermal-cardiogreen extravascular lung water (EVLW), thromboxane (TxB2), 6-keto-PGF1 alpha, PaO2, PaCO2 were determined every 30 min. Albumin flux was measured with scintigraphic determination of lung:heart radioactivity ratios versus time, called slope index (SI). At 3 hr, P produced marked (P less than 0.05) increases in PAP (18 +/- 7 to 37 +/- 2 mm Hg), TxB2 (471 +/- 513 to 9216 +/- 3615 pg/ml), 6-keto-PGF1 alpha, EVLW (6.4 +/- 1.4 to 14.6 +/- 5.7 mg/kg), and SI (0.4 +/- 0.2 to 1.7 +/- 0.5 X 10(-3) U/min) with decreases in PaO2 (214 +/- 47 to 101 +/- 41 torr), CO and SAP. Ibuprofen caused a rapid clearing of TxB2 and 6-keto-PGF1 alpha associated with a transient decrease in PAP; PaO2 was considerably improved compared to P; however, CO, SAP, EVLW, and SI were unaffected. Prostaglandin blockage temporarily ameliorated the pulmonary hypertension and markedly improved oxygenation in this porcine septic ARDS model, but failed to alter increased permeability, confirming other studies that the increased pulmonary shunt in ARDS is not only dependent upon capillary leak.

Experience with percutaneous transluminal coronary angioplasty (PTCA) of multiple vessels was reviewed to assess short-term outcome and long-term results. PTCA of multiple vessels was performed in 100 of the initial 500 patients (20%) who underwent PTCA at the Medical College of Virginia between July 1979 and August 1984. Eighty-nine percent had class 3 or 4 angina, and 66% had unstable angina. Two-thirds had severe stenosis of two vessels or major branches and one-third had three-vessel disease. One or more significant lesions were dilated in two vessels in 84 patients, in three vessels in 14 patients, and in four vessels in two patients. PTCA of 273 lesions (2.7/patient) was attempted (range two to eight per patient) with angiographic success in 250 lesions (91.6%). Primary success (angiographic and clinical improvement) was achieved in 95 of 100 patients (95%); 84% had success in multiple vessels, and 79% had success in all attempted lesions. Complications occurred in 11 patients (11%); four patients (4%) underwent urgent bypass surgery and four additional patients (4%) had myocardial infarction. Long-term results were assessed in 44 patients with primary success who had follow-up of more than 1 year (mean 26 months) after multiple-vessel PTCA. Twenty-eight patients (64%) remain event-free and improved and 48% are event-free and asymptomatic. Clinical recurrence developed in 15 patients (34%); four had sustained improvement with repeat PTCA, three remain improved with medical therapy, and eight (18%) have undergone bypass surgery during follow-up. One patient (2.3%) developed late myocardial infarction, and deaths have occurred in the follow-up cohort.(ABSTRACT TRUNCATED AT 250 WORDS)