Rationale of therapy in the patient with acute myocardial infarction and life-threatening arrhythmias: a focus on bretylium

Experimental evidence suggests a number of pathologic and electrophysiologic mechanisms that may help initiate ventricular arrhythmias accompanying myocardial ischemia and infarction. Early and late phase events are associated with reentry or an enhancement of focal mechanisms, or both. These can initiate ventricular tachycardia (VT) or ventricular fibrillation (VF), or both. The presence of distinct mechanisms that may initiate and maintain life-threatening dysrhythmias early in myocardial ischemia suggest different pharmacologic approaches for their prevention or suppression. Another consideration concerns patients subjected to coronary artery angioplasty or thrombolytic therapy and the development of arrhythmias associated with reperfusion of the once ischemic myocardium. The electrophysiologic mechanisms associated with reperfusion arrhythmias are unknown, and little is known about appropriate therapy for each episode of cardiac dysrhythmia. Ventricular extrasystoles or VT usually precedes VF. These premonitory arrhythmias are poor criteria for the institution of antiarrhythmic drug therapy, because VF develops within 1 to 10 minutes after the appearance of the rhythmic disturbances. Some authorities suggest that all patients with acute myocardial infarction should receive prophylactic antiarrhythmic therapy, because warning arrhythmias either do not occur at all or provide insufficient time to intervene pharmacologically. Many of the new class I antiarrhythmic agents effectively reduce the frequency of premature ventricular depolarizations, but lack specific antifibrillatory activity. However, the recent introduction of bretylium into clinical cardiology opens a new approach to preventing life-threatening ventricular dysrhythmias. Along with other members of class III, bretylium exerts different cardiac electrophysiologic effects than do the other 3 classes of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial perfusion imaging in humans by contrast echocardiography using polygelin colloid solution

This study evaluated the myocardial contrast effect and safety of polygelin colloid solution selectively injected into the coronary arteries in 25 patients during two-dimensional echocardiography. Six patients (group I) had selective intracoronary injections of nonagitated and 19 (group II) of hand-agitated polygelin colloid solution. Myocardial contrast was seen on two-dimensional echocardiographic cross sections in three patients of group I and in all patients of group II; in 16 patients it was also seen on M-mode echocardiograms. The contrast effect lasted for 15 to 60 seconds. The intensity of myocardial opacification was not significantly influenced by the amount of polygelin colloid solution injected, heart rate or cardiac size. The total number of contrast-enhanced segments after right and left coronary artery injections delineated the entire cross-sectional area in any given view. None of the patients developed symptoms during or immediately after the injections. One patient had transient second degree atrioventricular block after a right coronary wedge injection, one patient showed a QRS axis shift and two others had transient T wave changes. There were no aortic blood pressure changes and no significant serum enzyme (creatine kinase [CK], CK-MB fraction, glutamic oxaloacetic transaminase) elevation or alterations of left ventricular function assessed echocardiographically. It is concluded that hand-agitated polygelin colloid solution is a useful and safe intracoronary contrast agent for delineating myocardial perfusion areas on two-dimensional echocardiography in humans.     

Rest and exercise hemodynamic effects of sequential alpha-1-adrenoceptor (trimazosin) and beta-adrenoceptor (propranolol) antagonism in essential hypertension

The efficacy of acute beta blockade in essential hypertension is limited by reflex vasoconstriction. The aim of this study was to determine whether the latter response was modified by prior selective alpha-1-adrenoceptor blockade. A single-blind, within-patient, placebo-controlled evaluation of the immediate hemodynamic effects of sequential alpha-1 (trimazosin)- and beta (propranolol)-adrenoceptor blockade was undertaken in 10 men (34 to 58 years) with previously untreated essential hypertension. The study commenced with a 4-minute control period of constant-load (600 to 900 kpm/min) upright bicycle exercise, and measurements were made before (control) and 30 minutes after intravenous trimazosin (2 mg/kg) and exercise was then repeated; measurements at rest were again made 4 minutes after intravenous propranolol (0.2 mg/kg) before a final exercise period. Trimazosin at rest reduced systolic and diastolic arterial pressure and systemic vascular resistance without change in heart rate, cardiac output, or left ventricular (LV) filling pressure. During upright bicycle exercise the reductions in blood pressure were sustained without change in their rest-to-exercise increments. Other circulatory variables did not differ from control values. At rest the addition of propranolol further reduced systolic arterial pressure. Heart rate and cardiac output fell and systemic vascular resistance increased to its pretreatment control value. During exercise the changes at rest were sustained and the rest-to-exercise increments in blood pressure, heart rate, and cardiac output were reduced. LV filling pressure was significantly increased. In conclusion, alpha-1-adrenoceptor blockade modified the adverse effects of acute beta blockade at rest but not during exercise.     

New chemotherapy for patients with advanced hepatocellular carcinoma: Pilot study of β-interferon and doxorubicin one-shot intra-arterial chemotherapy

Background: Patients with advanced hepatocellular carcinoma (HCC) need an effective treatment modality because of the poor prognosis of the disease. From an in vitro study, beta-interferon (IFN-beta) has been reported to enhance the antiproliferative effects of doxorubicin on HCC cell lines. In the present study, we investigated the therapeutic effects of combined IFN-beta and doxorubicin intra-arterial injection therapy on patients with advanced HCC. Methods: IFN-beta (3 MIU) and doxorubicin (10 mg/bodyweight) were given by one-shot intra-arterial injection through an arterial port to patients with advanced HCC. One treatment course consisted of three intra-arterial injections per week for 4 weeks. Three courses were conducted and evaluation was done monthly. Results: Eleven patients with advanced HCC were treated with combined IFN-beta and doxorubicin. One patient enteredcomplete remission (CR), seven patients were evaluated as having stable disease (SD) and three as having progressive disease (PD). The mean overall survival was 10 months. The mean survival for CR and SD patients was 15 months, and that for PD patients was 6 months (P = 0.0464, log-rank test). Decrease of serum total bilirubin was observed for all patients. Conclusion: Combined IFN-beta and doxorubicin intra-arterial therapy offers an effective chemotherapy option for patients with advanced HCC by improving liver function and having tolerable side-effects.     

Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology’s (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC’s Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.     

Inhibition of interleukin-8 synthesis by intraarticular methotrexate therapy in patientes with rheumatoid arthritis

Summary 5 Patients with definite RA and knee effusions under constant doses of DMARD therapy were treated with up to 6 intraarticular injections of 10mg methotrexate (MTX) every 3 to 7 days. A matched randomized control group who received a single i.a. injection of 40mg triamcinolone hexacetonide (TC) was monitored according to the same protocol. The intraarticular granulocyte counts and IL-8 levels decreased in all MTX treated patients on day 10–13 and stayed low in those patients who could be re-evaluated after 13 weeks. Compared to the IL-8 levels, the other tested cytokine levels showed only minor changes on day 10–13. There was no need for re-injection in the TC group during the 13 week study phase. We conclude that intraarticular MTX therapy results in a strong decrease of SF-granulocyte counts. This effect may be due to the impairment of IL-8 mediated chemotaxis by decreased IL-8 synthesis in synovial fluid mononuclear cells. Clinically, repeated intraarticular MTX therapy results in a worse 13 week outcome than i.a. steroid treatment measured in an intention-to-treat analysis. Eingegangen: 14. April 1997 Akzeptiert: 15. Januar 1998     

Efficacy of ultrasonography-guided intra-articular steroid injection of the shoulder and excercising in patients with adhesive capsulitis: Glenohumeral versus subacromial approaches

Aim of the work

To evaluate the efficacy of intra-articular steroid injection of the shoulder joint with exercises in the management of patients with adhesive capsulitis and to compare glenohumeral (GH) versus subacromial subdeltoid (SASD) ultrasound-guided approaches.

Bacterial endocarditis with ruptured sinus of valsalva and aorticocardiac fistula

A case is presented of bacterial endocarditis with a ruptured sinus of Valsalva and formation of an aorticocardiac fistula from the right coronary sinus into the right atrium and right ventricle. The pathologic, clinical and surgical aspects of bacterial endocarditis complicated by a ruptured sinus of Valsalva and an aorticocardiac fistula are analyzed. This complication of bacterial endocarditis is still uncommon, but alertness to its diagnosis makes possible early and successful surgical treatment.     

Echocardiographic assessment of left ventricular outflow tract in d-transposition of the great arteries

The left ventricular outflow tract in 38 patients (aged 0.3 to 13 years) with complete d-transposition of the great arteries, 31 with intraatrial (Mustard) repair, was quantitated with echocardiography, and the findings were correlated with hemodynamic and angiographic data. The left ventricular outflow tract (LVO) was measured on the echocardiogram as an anteroposterior dimension between the closure point on the mitral valve below the pulmonary arterial root (PA) and the left endocardial surface of the interventricular septum. This measurement was expressed as an LVO/PA ratio and on the basis of these measurements three groups were recognized.Group I consisted of 14 patients who had an unobstructed left ventricular outflow tract and no significant pressure differences between the pulmonary artery and left ventricle. In Group II, the 16 patients had evidence of dynamic obstruction and mild to moderate pressure differences between the pulmonary artery and left ventricle, characterized in the echocardiogram by LVO/PA ratios comparable with those of Group I, but with an abnormally prominent early posterior systolic septal bulge in the left ventricular outflow tract, abnormal systolic anterior motion of the mitral valve and coarse fluttering of the pulmonary valve. In Group III the eight patients had anatomically fixed stenosis of the left ventricular outflow tract and severe left ventricular outflow pressure gradients characterized in the echocardiogram by a reduced LVO/PA ratio and fine vibrations of the pulmonary valve. Angiographically discrete or long segmental narrowing of the left ventricular outflow tract correlated well with the echocardiographic data. Echocardiographic measurements of left ventricular posterior wall thickness also correlated well with the severity of left ventricular outflow stenosis in these three groups. The echocardiogram provides clinically useful quantitative and qualitative analysis of the left ventricular outflow tract in patients with complete transposition of the great arteries.