Influence of cardiac output on peak t-PA plasma levels in patients receiving thrombolytic therapy with recombinant tissue-type plasminogen activator--correlation with patency rate.

We studied 35 consecutive patients with short onset of myocardial infarction who underwent thrombolytic therapy with rt-PA at a standard dosage regimen of 100 mg rt-PA total (10 mg given as a bolus followed by 50 mg, 20 mg and 20 mg per hour for 3 hours). These patients were monitored for t-PA antigen and t-PA activity and PAI-1 activity plasma levels during rt-PA infusion. Success or failure of thrombolytic therapy was evaluated by non-invasive criteria (early plasma creatine kinase peaks, early peak plasma myoglobin values, and electrocardiographic criteria) as well as by means of coronary angiography at the fourth day after thrombolytic treatment. In 24 (68.6%) of these patients a success of thrombolytic therapy could be established by these criteria, while 11 patients did not respond to thrombolytic therapy. Fifteen patients (14 responders and one non-responder) had to be excluded from the further evaluation because in these patients clinical laboratory data obtained upon admission before initiation of thrombolytic therapy were not complete. Therefore, 20 patients (10 responders and 10 non-responders) could further be analysed. The two groups of patients were not significantly different in body weight, body weight index, age, gender, liver or kidney functional parameters as determined before initiation of the thrombolytic therapy. Furthermore, PAI-1 plasma levels before initiation of thrombolytic therapy were not significantly different in the two groups, as were rt-PA dosage per body weight or body weight index.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction.

A decrease in the fibrinolytic potential, mainly due to an elevation of plasminogen activator inhibitor (PAI), has been described in patients with stable coronary artery disease and a previous myocardial infarction. We investigated plasma levels of PAI and tissue plasminogen activator (t-PA) and their possible circadian variations in patients with unstable coronary artery disease (CAD). Sixty-three patients were studied for at least 2 consecutive days during their stay at the coronary care unit (CCU). Diurnal plasma fluctuations in PAI and t-PA and onset of further myocardial ischemic episodes were monitored. As controls we used 22 age-matched patients submitted to the clinic because of non cardiac chest pain or valvular disease who revealed no evidence of CAD. PAI levels were significantly elevated in patients with unstable CAD (p less than 0.0001) but were not influenced by the extent of underlying CAD, history of previous myocardial infarction, known risk factors for CAD, or by extent of myocardial damage. The circadian variation of PAI levels with peak values between midnight and 6 A.M. found in controls was still present in patients but at a higher level. Preservation of circadian pattern in PAI plasma levels despite myocardial ischemic attacks indicates that elevation of PAI is rather not caused by a reactive phenomenon. On the other hand, elevated PAI levels and episodes of severe myocardial ischemia exhibiting a median time of onset at 10 A.M. seem to be closely related.

Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis.

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent or pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p less than 0.0001). In the CAD patients no significant variation in plasma PAI-1 values could be demonstrated when related to the extent of the disease or to a history of previous myocardial infarction. t-PA antigen was also elevated in CAD patients as compared to the non-CAD group (p less than 0.02). The results suggest therefore a strong correlation between coronary artery disease itself and elevated levels of components of the plasma fibrinolytic system.

A decrease in plasminogen activator inhibitor-1 activity after successful percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis.

To determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTCA), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p less than 0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p less than 0.05 to p less than 0.0005).

Reduction of infarct size induced by pressure-controlled intermittent coronary sinus occlusion.

The effect of pressure-controlled intermittent coronary sinus (CS) occlusion on myocardial infarction (MI) size was evaluated. A device for this purpose was developed that consisted of a balloon catheter and pump system that produced controlled, intermittent occlusion of the CS and used CS pressure as a feedback to determine the duration of occlusion. It was hypothesized that proper selection of occlusion and non-occlusion times would both facilitate improved retrograde flow to ischemic areas and allow for more complete venous washout of metabolites. In 13 treated dogs and 12 control dogs before treatment, myocardium at risk of MI was estimated by injection of technetium-labeled microspheres. Intermittent CS occlusion was then begun, 15 minutes after coronary artery occlusion, and continued until termination of the experiment 6 hours later. Postmortem determination of infarct size was performed using the triphenyltetrazolium chloride staining technique. Intermittent CS occlusion begun 15 minutes after coronary artery occlusion and continued for 6 hours resulted in a 45% average reduction in MI size (p less than 0.001). During CS occlusion, the sinus systolic mean pressure increased from 10 to 44 mm Hg, while the distal coronary artery mean pressure increased by an average of 36% (from 22 to 30 mm Hg, p less than 0.05). These results suggest intermittent occlusion may be an effective treatment for evolving MI. This therapy, used alone or combined with other therapies (e.g., administration of pharmacologic agents), appears to have great clinical potential.

Myocardial perfusion evaluated by contrast echocardiography. A preliminary report.

The usefulness of contrast echocardiography for demonstration of myocardial perfusion was studied on six mongrel dogs. Two contrast agents tested were: (1) 0.9 percent saline solution, and (2) CO2-enriched saline solution (containing 0.2 ml CO2/10 ml). Only the latter solution produced an elucidation of the myocardium and allowed an estimation of the distribution and flow velocity of the contrast agent, which was characterized using the following three parameters: (1) transmural flow time (0.13 +/- 0.02 s x +/- SEM); (2) circumferential flow time (1.43 +/- 0.31 s); and (3) persistence time (42.0 +/- 4.3 s). There were no serious side effects on hemodynamics or heart rhythm. Thus, contrast echocardiography offers the possibility of detecting and quantitating myocardial perfusion.

Decreased suppression of antibody-dependent cellular cytotoxicity by seminal plasma in unexplained infertility.

OBJECTIVE: To determine whether seminal plasma (SP) from unexplained infertile males has different suppressive activity on antibody-dependent cellular cytotoxicity (ADCC) than SP from fertile males or SP from males of couples with known infertility factor. DESIGN: Comparative clinical/experimental study. SETTING: In vitro fertilization program in a university hospital and a hospital research laboratory. PATIENT(S): A total of 245 SP samples from 174 infertile and 16 fertile couples were compared. INTERVENTION(S): SP suppression of ADCC was measured by using human 51chromium-labeled red blood cells (RBC), sensitized with IgG-rabbit-anti-human-RBC as targets and peripheral blood lymphocytes as effector cells. MAIN OUTCOME MEASURE(S): Suppressive activity of each sample was determined by calculating 51Cr-release in the presence and absence of SP. RESULT(S): When analyzed with respect to sperm number, motility, and morphology, suppressive activities of samples with normal semen analyses (n = 142) were significantly higher (x = 37% +/- 14%) than suppressive activities of abnormal samples (n = 103; x = 32% +/- 13%). There was no strong correlation of suppressive activity to other semen parameters. Within the andrologically normal males, SP from the unexplained infertile couples (n = 15) showed significantly lower suppressive activity (x = 24% +/- 11%) compared with the SP from fertile males (n = 16; x = 35% +/- 13%) and from couples with female infertility factor (n = 65; x = 39% +/- 14%). CONCLUSION(S): Loss of suppressive activity is associated with unexplained infertility, even in male patients who previously were considered normal by traditional methods of semen analysis.

Heparin induced increase of t-PA antigen plasma levels in patients with unstable angina: no evidence for clinical benefit of heparinization during the initial phase of treatment.

Patients with unstable coronary artery disease were randomly treated either with a combination therapy consisting of nitrates and calcium-channel blockers without or with addition of clinical grade heparin administered subcutaneously; in order to evaluate the effect of heparin treatment on the fibrinolytic system, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels were related to the clinical course of the disease. In heparinized patients thrombin time was prolonged more than 3-fold the normal range indicating effective heparin treatment. Heparinization led to a significant increase in t-PA antigen plasma levels (p less than 0.0001) within approximately four hours while PAI-1 activities remained unaltered. However, the measurable increase of the anticoagulant and pro-fibrinolytic activities of heparin did not result in a short-term benefit for the heparinized patients because the number of further ischemic attacks per patient during the observation period of three days was not different between the two study groups.

Assessment of regional wall motion in coronary artery disease using radionuclide methods.

72 patients with CAD, 10 patients with congestive cardiomyopathies and 10 normal subjects were evaluated by radionuclide angiography. Comparison with contrast angiography showed good results for LVEF (r = 0.83). Regional asynergies observed in the radionuclide angiography correlated well with defects in thallium scintigrams. Extent of abnormal wall motion was measured and compared with normals, appreciating the deviation from the normal mean radial shortening. Good correlation could be demonstrated with radionuclide ventriculography. In 80% of congestive cardiomyopathies the right ventricle wall became visible in the thallium scintigram.

Radionuclide assessment of cardiac performance and myocardial perfusion in congestive cardiomyopathies.

To determine the reliability of radionuclide techniques in the diagnosis of congestive cardiomyopathy (COCM), the function of the right ventricle (RV) and left ventricle (LV) was evaluated in 32 patients with COCM and 21 normal subjects using radionuclide angiography (first pass and gated blood pool scan) combined with quantitative 201 thallium (Tl) myocardial perfusion imaging. In COCM parameters of RV and LV performance were significantly reduced (p less than 0.01); regional wall motion analysis revealed a reduced radial shortening ability (p less than 0.05). 201 Tl distribution within the myocardium was not different between COCM and N; however, segmental 201Tl-uptake was significantly reduced (p less than 0.01). RV free wall was visualized on 201Tl scan in 80% of patients with COCM. There was no correlation between RV free wall visualization and RV hemodynamics. Thus these scintigraphic aspects provide an atraumatic and sensitive technique for the evaluation of patients with COCM.

Chylopericardium: a rare cause of pericardial effusion.

A 21 year old man presented with asymptomatic, isolated chylopericardium. Despite echocardiography, radionuclide-angiography, computer tomography, and chemical analysis of the chylous effusion, the etiology remained obscure. After patent blue dye infusion into peripheral soft tissues, the appearance of coloring material in the effusion at 4 hours suggested direct communication of the pericardium with an apparently large thoracic duct. Fifteen months later, cardiomegaly persists in site of medium-chain triglyceride dietary restriction.

[R spike potentials in ergometric stress: patients with dilated cardiomyopathy in comparison to coronary heart disease]. / R-Zackenpotentiale unter ergometrischer Belastung: Patienten mit dilatativer Kardiomyopathie im Vergleich mit koronarer Herzkrankheit.

R-wave amplitude changes during exercise were compared in patients with cardiomyopathy (n = 32), patients with coronary artery disease (n = 58) and controls (n = 12). Patients with cardiomyopathy (CMP) had a smaller R-wave amplitude (RWA) at rest than those with coronary artery disease (CAD). At comparable levels of exercise patients with CMP showed no change in RWA, while those with CAD demonstrated an increase in RWA. Controls showed a decline in RWA. In patients with CAD changes in RWA during exercise were more sensitive in the detection of disease than ST-segment changes. Left ventricular function was the major determinant of the direction and magnitude of RWA changes both in patients with CMP and CAD, with lesser changes in RWA in patients with more severely reduced left ventricular function.

[A study of a swimming training programme in the rehabilitation of patients following myocardial infarction (author's transl)]. / Erfahrungen mit Schwimmen zur Bewegungstherapie nach Myokardinfarkt.

A special swimming programme was initiated during the course of rehabilitation of patients after myocardial infarction with additional disturbances of the musculoskeletal system. Allowance was made for aspects of individual training requirements. Patients were divided in two groups according initial values of physical working capacity: One group contained patients with less than 80% of the normal work capacity, the other those with borderline normal values. The first group showed an average increase of 35% in the initial values during a one-year period of swimming training once a week. The other group with practically normal initial values showed only a slight or negligible increase. Serum lipid levels were unchanged in both groups. No serious side effects were encountered in more than 3000 patients hours. However, no prediction of the risks of this type of training as compared to other forms of physical exercise in patients recovering from myocardial infarction can be made from this study.

[Myocardial revascularization in threatening extension of myocardial infarction (author's transl)]. / Koronarchirurgie beim drohenden Infarktnachschub.

Myocardial revascularization was performed in 13 patients between two and 14 days following initial infarction because of impending re-infarction. The diagnosis of impending re-infarction was made on the basis of the following criteria: myocardial infarction; repeated stenocardia despite medical treatment; renewed ST-T changes in the ECG. The intra-aortic balloon pump was installed in 7 patients for haemodynamic reasons (shock, massively raised pressure in the pulmonary artery). 12 patients survived the surgical intervention and were eventually discharged free of stenocardia. The presented findings suggest that surgical intervention in impending re-infarction appears of value in those cases which have not been satisfactorily controlled by conventional medical treatment.