Gemfibrozil decreases platelet reactivity in patients with hypercholesterolemia during physical stress.

The effects of the lipid-lowering drug gemfibrozil on platelet reactivity at rest and during submaximal exercise were investigated in 10 patients with serum cholesterol levels greater than 270 mg/dl. No significant changes were observed in platelet reactivity at rest after gemfibrozil treatment. However, a marked decrease in platelet reactivity was seen in almost all patients treated with gemfibrozil during exercise. The adrenaline concentration necessary to induce secondary aggregation increased in eight patients during exercise after gemfibrozil and in two after placebo treatment. When adenosine diphosphatase (2 to 4 mumol/L) was used to induce aggregation, 5-hydroxytryptamine (serotonin) and thromboxane B2 secretion by platelets decreased by 35% and 67%, respectively, during exercise in patients treated with gemfibrozil. The area under the aggregation curve decreased by 28% during exercise after gemfibrozil. No significant changes occurred in these variables during exercise after placebo. Thus, gemfibrozil seems to have antiplatelet effects that might have importance in the prevention of acute complications of atherosclerosis in patients with hypercholesterolemia.

Right gastroepiploic artery as a coronary bypass graft.

Between November 1987 and April 1988, the right gastroepiploic artery (GEA) was used as a coronary artery bypass graft in 11 patients, 9 men and 2 women. In 1 of them, the GEA was used because no veins were available; in the others, the GEA was used to avoid the use of vein grafts. The GEA was anastomosed to the right coronary artery in all patients, and internal mammary artery grafts were used to bypass the left anterior descending and circumflex coronary arteries. All patients survived the operation. There were no early and, to date, there have been no late complications of the abdominal component of the operation. Postoperative coronary angiography showed a patent right GEA in 9 patients (82%). In 1 patient the GEA was occluded, probably because of an enlarged liver. If the long-term patency of right GEA grafts is similar to that of internal mammary artery grafts, wider use of this viable graft is indicated.

Studies on ergometer exercise testing. II. Effect of previous myocardial infarction, digoxin, and beta-blockade on exercise electrocardiography.

The results of exercise electrocardiography were studied in a random sample of 317 subjects with clinical suspicion of coronary artery disease. In 278 patients with coronary artery disease the rate of false negative tests was 18% with and 12% without previous myocardial infarction. If ST elevation was considered a negative response, the corresponding values were 25% and 13%, respectively, p less than 0.01. The greatest prevalence of negative tests was seen after anterior myocardial infarction: 27% or 42% when ST elevation was not included into positive responses. The sensitivity of exercise-induced ST depression for the presence of multivessel disease was lower after anterior infarction (67%) than in other patients with previous infarction (86%), p less than 0.01. The corresponding specificities were 71% and 22%, respectively, p less than 0.005. If ST elevation was included into positive responses these differences were abolished. In subjects without myocardial infarction the sensitivity was 89% and specificity 43%. Digitalized patients had somewhat higher sensitivity in the exercise electrocardiogram than those without digoxin, 90% vs. 81% (p less than 0.05), but the difference was not seen with exclusion of ST elevation. The specificity was not influenced by digitalis. beta-blockade had no effect on the sensitivity or specificity, but the prevalence of postexercise ST evolution was lower with (11%) than without (30%) beta-blockade. The prevalence of slowly ascending ST depression was reduced by three factors: the presence of digitalis in patients without previous myocardial infarction, infarction itself, and the extent of coronary artery disease. We conclude that exercise electrocardiography has only a limited value in prediction of multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on ergometer exercise testing. I. Significance of the type of ST-segment response, sex, and chest pain.

Ergometer exercise electrocardiographic (EECG) data were surveyed in a series of 328 patients (277 men and 51 women) subjected to coronary arteriography. The sensitivity and specificity of EECG for coronary artery disease (CAD) were 84% and 54%, respectively. The predictive accuracy of a positive test for CAD was 95% in men and 81% in women. The predictive accuracy of a negative test was 25% in men and 62% in women. When slowly ascending ST depression was considered insignificant, the sensitivity of EECG declined to 71%, with an increase in specificity to 64%. CAD was present in 89% of the patients with slowly ascending ST depression and 65% of them had a multivessel disease. Seventy-two subjects had postexercise ST-segment elevation. The predictive value of this sign for CAD was 94%. Exercise-induced chest pain had quite a similar diagnostic significance as EECG. The prevalence of CAD in patients with a history of typical angina was 94% in both sexes. Atypical chest pain was associated with normal coronary arteriography in 59% of males and 100% of females.

Coronary collateral circulation.

The occurrence and influence of coronary collateral circulation and obstruction of the supplying coronary arteries on left ventricular contractility, prevalence of myocardial infarction, and bicycle exercise ergometer test were studied in a random sample of 286 patients with angiographically documented coronary artery disease. Collaterals appeared increasingly in all three main coronary arteries with grade of obstruction. The highest prevalence of collaterals occurred in stenosis of the right coronary artery (60%), followed by the left descending artery (45%); they occurred least in the left circumflex artery (21%) (p less than 0.001). The frequency of intra-arterial collateral circulation was 42%, 11%, and 12%, respectively (p less than 0.001). With total occlusion of the left anterior descending coronary artery, 22% of the patients had normokinetic anterior and apical left ventricular wall when collaterals were present. More often, the inferior wall showed normal contraction with total occlusion of the right coronary artery and collaterals [52%, p less than 0.001 compared with left anterior descending artery (LAD)]. The prevalence of inferior myocardial infarction was 39%, with collateral circulation to the totally occluded right coronary artery. The respective prevalence of anterior infarction and total occlusion in the left coronary artery was 58% (p less than 0.02). The presence or absence of collaterals had no obvious influence on ST-segment response during bicycle ergometer test. In triple-vessel disease, peak work capacity was better when collaterals to LAD were not jeopardized (427 kpm) than when jeopardized (321 kpm) (p less than 0.02).

Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion.

The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the ß1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis.

Hemoperfusion in quinidine intoxication.

A case report on quinidine intoxication is presented. After having ingested 8.1 g quinidine the patient had clinical and ECG signs of a severe intoxication and a serum quinidine level of 8.5 mg 1. She was treated for six hours with charcoal hemoperfusion. Serum quinidine was on an average 36% lower after than before the cartridge. The mean quinidine clearance of hemoperfusion was 24 ml/min. All clinical and ECG signs of quinidine intoxication were normalized during hemoperfusion. The data justify that hemoperfusion is probably the best way to treat severe quinidine intoxication.

Effect of isometric exercise and autonomic blockade on the haemodynamics: a noninvasive study in healthy volunteers.

Sixteen healthy young volunteers were studied with echocardiography and systolic time intervals at rest and after three minutes' isometric exercise before and during autonomic blockade with atropine and propranolol. Isometric exercise increased cardiac output by raising the heart rate from 64 +/- 3 to 72 +/- 4 bpm (SEM) (p less than 0.01). Mean blood pressure increased from 86 +/- 2 to 104 +/- 3 mmHg (p less than 0.001) without any changes in the calculated total peripheral vascular resistance. Afterload (left ventricular systolic wall stress) rose but preload (left ventricular end-diastolic diameter, LVEDD) did not change. There was no variation in fractional shortening, maximal velocity of circumfertial fibre shortening (VCFmax) or pre-ejection period (PEP) despite increased afterload. This indicates stimulated intropy during isometric exercise. Autonomic blockade enhanced cardiac output by increasing heart rate from 64 +/- 3 to 97 +/- 2 bpm (p less than 0.001). Mean blood pressure rose from 86 +/- 2 to 93 +/- 2 mmHg (p less than 0.01) while vascular resistance fell. Afterload did not change but LVEDD shortened form 45.5 +/- 0.9 to 43.5 +/- 0.9 mm (p less than 0.001). Preload-independent VCFmax did not increase despite raised heart rate. PEP rose from 99 +/- 4 to 107 +/- 3 ms (p less than 0.01) and fractional shortening fell from 29 +/- 1 to 25 +/- 1% (p less than 0.001); these changes were greater than expected from the reduced preload. Consequently autonomic blockade seems to impair myocardial contractility despite vagal dominance at rest. Heart rate and cardiac output were not influenced by isometric exercise during autonomic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous digoxin blunts the rise of inotropy induced by isometric exercise: a noninvasive study in healthy volunteers.

Nine healthy volunteers were studied with echocardiography and systolic time intervals at rest and after 3 minutes' isometric exercise by hand grip. The recordings were repeated after intravenous administration of 1 mg digoxin before and after autonomic blockade induced with atropine and propranolol. During hand grip the heart rate rose from 61 +/- 3 (mean +/- SEM) to 73 +/- 5 bpm (p less than 0.05). Afterload, i.e. left ventricular systolic wall stress, increased by 21% from 260 +/- 19 x 10(3) dyn/cm2 (p less than 0.05). Preload, i.e. left ventricular end-diastolic diameter (LVEDD), fractional shortening and the ratio of the pre-ejection period to the left ventricular ejection time (PEP/LVET) did not change, indicating increased contractility. After digoxin heart rate rose during handgrip from 50 +/- 2 to 65 +/- 5 bpm, and wall stress increased by 19% from 274 +/- 21 x 10(3) dyn/cm2 (p less than 0.01 for both). Even though LVEDD rose from 44.8 +/- 1.4 to 46.6 +/- 1.3 mm (p less than 0.05), fractional shortening decreased from 33 +/- 2 to 30 +/- 2% (p less than 0.05) and PEP/LVET increased from 0.292 +/- 0.014 to 0.327 +/- 0.014 (p less than 0.01). This suggests that autonomic reflexes due to digoxin obscured the increase in inotropy during static exercise. Autonomic blockade raised heart rate under digoxin from 50 +/- 2 to 90 +/- 4 bpm and mean blood pressure from 87 +/- 2 to 99 +/- 3 mmHg (p less than 0.001 for both) without changes in loading conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic and clinical features of tricyclic antidepressant intoxication. A survey of 88 cases and outlines of therapy.

The data of 88 consecutive patients with intoxication due to tricyclic antidepressant drugs were retrospectively surveyed. Apart from sinus tachycardia, temporary electrocardiographic changes developed in 48 patients (55%). These included, in order of their frequency, QTc prolongation (85%), T-wave abnormality (82%), PQ prolongation (19%), widening of QRS with or without bundle branch block pattern (19%), and supraventricular or indefinable tachycardia with wide QRS complexes (8%). The clinical course was more severe in patients with electrocardiographic changes. They were more frequently unconscious and more often required assisted ventilation than those without electrocardiographic changes (p less than 0.001). Hypotension developed in 6 patients within the first hours of poisoning; all had repolarization abnormalities and 3 developed paroxysmal supraventricular tachycardia with aberrant ventricular conduction. All 88 subjects made a good recovery and no haemodynamic problems occurred after the first 12 hours of intoxication. Second and third degree atrio-ventricular block, bradyarrthythmias and asystole were not seen in any of the patients. A prophylactic cardiac pacemaker was inserted in 13 patients with wide QRS complexes and/or prolonged PQ interval, but was never needed for bradyarrhythmias or overdrive pacing.

Acute renal failure following nontraumatic rhabdomyolysis.

The etiology and clinical course of acute nontraumatic rhabdomyolysis and ensuing renal failure was surveyed in a series of 40 consecutive patients. In 28 cases the muscle damage occurred after excessive consumption of ethyl alcohol and/or other intoxications. Prolonged lying immobilized was the reason or contributing factor for rhabdomyolysis in 22 cases. The other evident etiologies were convulsions, vigorous physical exercise, arterial occlusion and hypothermia. Typical local signs of rhabdomyolysis--pain, swelling and weakness of the affected muscles--were absent in one fourth of the patients. In these cases the diagnosis was based on transient elevation of serum creatine kinase enzyme activity. Dialyses were required to manage acute renal failure in 24 subjects. All 36 survivors recovered normal renal function. Neurological defects in the extremities still persisted in 16 patients at three months' follow-up.

Effect of digoxin on the heart in normal subjects: influence of isometric exercise and autonomic blockade: a noninvasive study.

1. Eight healthy subjects were studied before digoxin and after successive therapy periods of 1 week 0.125, 0.25 and 0.50 mg of digoxin. The mean serum concentrations (+/- s. d.) were 0.4 +/- 0.2, 0.6 +/- 0.3 and 1.4 +/- 0.5 nmol l-1, respectively. The effects of digitalis were studied by echocardiography and systolic time intervals at rest and after 3 min handgrip exercise. Effects of simultaneous autonomic blockade induced by atropine and propranolol were also examined. 2. Digoxin in increasing doses slowed the heart rate at rest; with the daily dose of 0.50 mg from 63 +/- 10 to 53 +/- 6 beats min-1, and fractional shortening rose from 28 +/- 6 to 33 +/- 3% (P less than 0.05 for both). Preload, afterload and cardiac output did not change. The electromechanic systolic time index (QS2I) decreased (P less than 0.001) and the observed alteration of QS2I was dose-related. 3. The influence of digoxin was similar during isometric exercise, except for unchanged fractional shortening. 4. During autonomic blockade digoxin slowed the intrinsic heart rate from 93 +/- 6 to 86 +/- 6 beats min-1 (0.25 mg) and to 83 +/- 6 beats min-1 (0.50 mg) (P less than 0.01 for both). QS2I was shortened (P less than 0.01). Echocardiographically determined ejection phase indices remained unchanged. 5. When handgrip stress was induced during autonomic blockade, digoxin evoked a clearcut increase in contractile function, resembling the effects of digoxin alone at rest. Thus, fractional shortening increased by 14% and QS2I decreased by 16 ms (P less than 0.01 for both). 6. We conclude that digoxin increases the contractility in normal heart without changes in loading conditions. The rise in inotropy at rest is obvious from both fractional shortening by echo and systolic time intervals. The same takes place during handgrip with autonomic blockade, when the heart lacks sympathetic support. The influence of long-term digoxin on heart rate is partly direct without autonomic mediation. The effect of digoxin is dose-dependent.

Acute renal failure caused by alcohol-induced rhabdomyolysis.

5 cases of severe acute renal failure caused by ethyl alcohol-induced rhabdomyolysis are reviewed. 4 patients were dialyzed. All patients recovered completely from the renal failure.

Overdrive pacing as treatment of sotalol-induced ventricular tachyarrhythmias (torsade de pointes).

Four patients with ventricular arrhythmias due to sotalol intoxication were successfully treated with overdrive pacing. In three patients the reason for sotalol overdose was a suicidal attempt and in the fourth patient the reason was unknown. In all cases a prolongation of the Q-T interval was seen, which is a typical feature of sotalol overdose. Other features of beta-blocker intoxication like bradycardia were found in all patients and hypotension in two patients. Three of four patients received lidocaine, but with no effect on multiple ventricular premature beats (VPB) or ventricular tachycardia (VT) of "torsade de pointes"-type. Overdrive pacing abolished immediately VPBs and VTs in three patients, and in the fourth patient there was apparent decrease in dysrhythmia. Temporary overdrive pacing is suggested as treatment of ventricular arrhythmias in association with prolonged Q-T interval caused by overdose of sotalol.

Haemodynamic effects of atenolol and bopindolol at rest and during isometric exercise. A non-invasive study in healthy volunteers.

Circulatory effects of bopindolol, a new nonselective beta blocking agent with intrinsic sympathomimetic activity and atenolol were compared. After baseline and first dose measurements atenolol 25 mg twice daily and bopindolol 1 mg daily were given to 10 healthy young subjects. Haemodynamic measurements were made noninvasively using echocardiography and systolic time intervals. Clinical and circulatory indices were measured at baseline, after initial dose and after one week of regular treatment at rest and at isometric handgrip exercise (IE) (HG). Atenol reduced the heart rate from 62 bpm to 49 and blunted totally the HR increase during IE (p less than 0.01). Bopindolol caused a 10% fall in heart rate (NS) at rest and a 15% fall (p less than 0.05) during IE. BP fell by 6% after atenol administration and 4% after bopindolol (NS) at rest and similarly during IE. In contrast to bopindolol, atenolol caused small increases initially in left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD). A 10% increase in FS was seen at rest after bopindolol administration (NS). With the fall in heart rate the estimated cardiac output (CO) also fell from 3.66 to 3.151/min (P less than 0.05) after atenolol but rose from 3.87 to 3.93 after bopindolol (NS) during chronic treatment. Consecutively the total peripheral resistance (TPR) was increased to some extent by atenolol, whereas bopindolol reduced it at rest and during IE. A similar response was also found in systolic time intervals PEP/LVET which were reduced during bopindolol administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic effects of bopindolol and atenolol in coronary artery disease. A noninvasive study.

Bopindolol, a new non-selective betablocker, and atenolol, a conventional betablocker, were studied in parallel groups of eight normotensive patients with NYHA II-III angina pectoris. Non-invasive haemodynamic measurements were made using echocardiography and systolic time intervals. Drug doses were 1 mg bopindolol and 100 mg atenolol once daily; measurements were made immediately and at one and six weeks intervals. Both drugs reduced heart rate, atenolol from 62 to 47 beats/minute (24%, P less than 0.01) and bopindolol from 64 to 56 beats/minute (13%, P less than 0.05) at 24 hours. Only atenolol reduced mean blood pressure. Rate pressure product was persistently reduced by atenolol (30% at 24 hours), while with bopindolol this effect lessened with time. Opposite trends in left ventricular enddiastolic and endsystolic diameters were observed; with atenolol tending to increase and bopindolol to lower them. Atenolol had no influence on cardiac contractility, while bopindolol increased it, which was shown by enhancements in the fractional shortening, ejection fraction and maximum velocity of fibre shortening. Neither drug changed peripheral vascular resistance or systolic time intervals. Two patients on bopindolol left the study because of worsening symptoms of coronary artery disease, and two on atenolol owing to side effects, bradycardia and syncope in one and diarrhea in the other. In conclusion, bopindolol showed less beta-blocking effect than atenolol and it had a positive inotropic effect. Its benefit in treating coronary artery disease remains to be proved.

Increase of cardiac output by afterload reduction in patients with severe congestive heart failure using nitroglycerin discs. A double-blind placebo-controlled haemodynamic study.

In a double-blind crossover study, the haemodynamic effects of nitroglycerin discs were compared with placebo in 9 patients with severe chronic congestive heart failure. Hourly measurements were made throughout 24 hours for the placebo and the active treatment; the first 6 hours were used as a dose titration phase to achieve at least a 5 mmHg decrease in pulmonary arterial diastolic pressure. Active treatment, requiring 30 mg of nitroglycerin in most patients, produced a significant improvement in the cardiac index compared with placebo, as assessed from the end of the dose titration period to the 24th hour. Values determined as baseline, as the average from hour 7 to 24, and at the 24th hour for active discs were 2.3, 2.5 and 2.6 litres/min/m2, whereas for the placebo they were 2.3, 2.2. and 2.2 l/min/m2, respectively. Heart rate remained unchanged during the study, though mean systemic arterial blood pressure and vascular resistance were lower during active treatment. Right atrial and pulmonary arterial pressures did not change. In conclusion, nitroglycerin discs decrease afterload and improve cardiac performance over 24 hours in patients with heart failure.