Acute effect of various doses of isosorbide-5-mononitrate on hemodynamic and exercise performance in coronary artery disease.

The optimal dose of nitrates is still controversial, as chronic usage of too high a dose may result in a decrease in vascular response. The dose should be determined to reduce preload acutely, and not to decrease the activity during chronic therapy. To determine this dose, 50 patients with angiographically confirmed coronary artery disease were studied. The effects on heart rate and mean systemic and pulmonary arterial pressures at rest and during exercise, and work capacity and duration were measured. The patients were classified into 5 groups, receiving placebo or isosorbide-5-mononitrate, 5, 10, 20 and 50 mg, respectively, as a single oral dose. Placebo had no effect on the measured parameters. All doses of isosorbide-5-mononitrate reduced mean pulmonary arterial pressure: 10 mg--by 16% at rest and 24% during exercise; 20 mg--24% and 34%, respectively (a near maximal effect); and 50 mg--27% and 38%. Similar results were found also for work capacity: 10 mg increased work capacity by 33%; 20 mg--79%; and 50 mg--56%. Thus, the therapeutically optimal single dose is about 20 mg. Higher doses produce no additional benefit and increase the risk for tolerance development.

Interval treatment of coronary artery disease with sustained-release isosorbide-5-mononitrate.

The possibility of maintaining preload reduction and enhancement of exercise tolerance during an interval treatment with 50 mg/day of sustained-release isosorbide-5-nitrate (IS-5-N) was investigated in 13 patients (aged 54.4 +/- 7.9 years [mean +/- standard deviation]) with angiographically confirmed coronary artery disease and chronic stable angina pectoris. The effects of a single dose (acute test) were compared with those following an 8-day (chronic) regimen of mononitrate administration. Two hours after administration of 50-mg sustained-release IS-5-N, mean resting pulmonary arterial pressure (PAP), measured with a Swan-Ganz catheter, was reduced by 27% (p less than 0.01), and at submaximal exercise level (50 W, 3 minutes) by 34% (p less than 0.001). At individually highest comparable work loads mean PAP was reduced by 28% (p less than 0.01), and at maximal work load the PAP reduction was 21% (p less than 0.05). At the end of 1 week of therapy with sustained-release IS-5-N a slight, clinically irrelevant reduction of hemodynamic effects was recorded. Work capacity increased after 1 hour by 60% (408 +/- 104 vs 653 +/- 147 W x min, p less than 0.001)--still significantly above baseline 10 hours after nitrate administration. No difference from baseline was demonstrable 24 hours after medication. During interval therapy the improved work capacity was fully maintained (chronic, 1 hour: 417 +/- 93 vs 679 +/- 160 W x min, p less than 0.001). During interval therapy with sustained-release IS-5-N, hemodynamics and exercise tolerance were durably improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99m-HMPAO brain SPECT in patients with syndrome X.

Ninety-five patients with syndrome X were studied by brain single-photon emission computed tomographic examination; 72 (76%) had pathologic findings suggestive of cerebral perfusion abnormalities. These findings support the hypothesis of a vascular disorder not confined to cardiac vessels.

Myocardial infarction as a complication of dobutamine stress echocardiography.

Only few cases of myocardial infarction complicating dobutamine stress echocardiography have been reported. We observed a 42-year-old woman in whom acute inferior wall infarction developed 10 minutes after discontinuation of dobutamine stress echocardiography with up to 20 micrograms/kg/min dobutamine. The right coronary artery, which had had a 50% stenosis in the prior angiography, showed proximal complete occlusion on the immediately performed recatheterization. Thrombolysis in myocardial infarction study flow grade 3 was rapidly accomplished by intracoronary thrombolysis with recombinant tissue type plasminogen activator. For recurrent unstable angina, the patient received coronary bypass grafting on the same day. The case shows that myocardial infarction not preceded by regional wall motion abnormalities is a possible complication of dobutamine stress echocardiography. Post-test monitoring even after negative tests is recommended.

The current state of extracorporeal haemorheotherapy: from haemodilution via cascadefiltration to rheohaemapheresis.

Rheological therapy aims at an improvement of organ perfusion however, it has to be stressed that the tonus of the blood vessels also plays an important role for both the blood distribution and the rheology in the micro- and the macrocirculation. Conventional rheotherapy consists of attempts to influence nutrition and life style, to apply drugs such as purin derivatives, vasodilatating or defibrinising substances and hypervolaemic (using infusion therapy), hypovolaemic, e.g., blood letting, erythrocytapheresis and--the most widely distributed- -isovolaemic haemodilution. With the introduction of centrifugal devices, and approximately 10 years later with the introduction of hollow fibre and flat sheet membrane techniques, a considerable increase of therapeutical efficacy was achieved. These technologies were successfully applied for the treatment of cellular and plasmatic hyperviscosity syndromes. The treatment of less severe diseases of the micro- and macrocirculation, vessel stenosis, vessel wall sclerosis, malformation of the blood vessel architecture, pathological clinical-chemical blood parameters and maldistribution have hardly been taken into consideration. Our group at Köln investigated different plasma differential separation techniques and demonstrated, that adsorption as well as filtration could be applied. These different techniques being 6-10 times more effective as conventional haemodilution techniques have in common high molecular weight proteins determining the viscosity of plasma and thus whole blood viscosity is removed, however differences among the different elimination techniques do exist. The rheological and clinical importance of such differences has to be determined. Applying filtration techniques for both primary and secondary separations, the concept of Rheohaemapheresis was developed. A corresponding quality program was also introduced into our clinical routine. Rheohaemapheresis is supported from the currently introduced concept of the synergetic consideration of the microcirculation. Age related macular degeneration, so far without generally accepted therapy, is a most advanced indication based on several pilot studies and a prospective, randomised controlled trial. Other diseases of the microcirculation have also successfully been treated.

[Fibrinolytic therapy of deep vein thrombosis]. / Lysetherapie bei tiefen Beinvenenthrombosen.

BACKGROUND: The most important complications of deep vein thrombosis are pulmonary embolism and postthrombotic syndrome. While the medicine of lethal pulmonary embolism is reduced to less than 2% by conventional anticoagulation, fibrinolytic therapy aims at a reduction of the greater than 50% incidence of postthrombotic syndrome. The optimal therapeutic regimen concerning risks and effect has not been established yet. RESULTS: A review of 26 studies involving ultrahigh-dose streptokinase (UHSK), urokinase (UK), and tissue-type plasminogen activator (rt-PA) shows the highest success rate for UHSK (45% complete and 40% parital patency), whereas there are lower rates for UK (25% and 40%) and low-dose locoregionally applied rt-PA (22% and 44%). The studies were not directly comparative, however. Published data concerning complications range from 1.7% mortality for UHSK to 0.9% for UK and 0.0% for rt-PA. Success criteria, however, are varying and not well defined. The influence of fibrinolytic therapy on the incidence of postthrombotic syndrome has not been established prospectively, but a reduction by 40 to 50% can be assumed. Calf vein thromboses are not indication for lytic therapy. In patients with iliacal vein thromboses there is an increased risk of pulmonary embolism using UHSK. CONCLUSIONS: UHSK can be regarded the standard concerning success rate in deep vein thromboses. DATA involving locoregional therapy with rt-PA are inconsistent and worse, but bleeding complications might be less frequent. Large prospective studies evaluating the impact on incidence and severity of the postthrombotic syndromes, which involve a controlled application of compression therapy are needed.

[Hemodynamics and differentiated CO transfer following fulminant lung embolism and pulmonary artery embolectomy and following recurrent lung embolism]. / Hämodynamik und differenzierter CO-Transfer nach fulminanter Lungenembolie und Pulmonalisembolektomie sowie nach rezidivierenden Lungenembolien.

Pulmonary embolectomy as an emergent surgical treatment after massive pulmonary embolism often is necessary in cardiogenic shock (CS) and even without previous diagnostic. If complete dissolution of the thromboembolus is possible or spreading of microemboli may occur is unknown. Therefore we studied 21 patients surgically treated by embolectomy, ten of these with consecutive cardiogenic shock (CS) and twelve patients after repetitive microembolism and cava-blocking. Besides lung-functional parameters for special CO-diffusion capacity (DLCO), differentiated in membrane (DM) and vascular (VC) component (Roughton and Forster), we measured mean pulmonary artery pressure (PAP) at rest and at exercise. Patients after repetitive embolism showed considerably more diminution of DLCO (-31%) than those after single massive embolic event (-15%) even concomitant by CS (-10%). Repetitive microembolism lowered VC by 21%. Slight decrease of DM was found after CS. Mean pulmonary artery pressure was elevated at rest (26 mm Hg) and exercise (33 mm Hg) after repetitive microembolism and normal after massive embolism or CS. Pulmonary embolectomy may prevent disturbances of DLCO or PAP even after CS. Damage of vascular integrity (VC) was found after microembolism. Pulmonary embolectomy seems to remove total embolic material and therefore seems to be optimal.