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Thrombolytic treatment during cardiopulmonary resuscitation is thought to reverse the cerebral no-reflow phenomenon which is widely considered to limit neurological recovery after prolonged cardio-circulatory arrest. However, the recent multicenter randomized double-blind TROICA (Thrombolysis in Cardiac Arrest) trial revealed that patients with witnessed out-of-hospital cardiac arrest did not experience an improvement of neurological outcome when treated with the throm-bolytic agent tenecteplase [1]. This raises the question of the importance of coagulation disturbances in the pathophysiol-ogy of no-reflow and its reversal by thrombolytic interventions. This article provides an overview of the experimental literature on this subject.

The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II-III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg X min for 4 h, with an interval of 2-3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5-2.0 ng/kg X min iloprost, indicating that iloprost reduced platelet stimulation by 50%-70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg X min. It is concluded that iloprost administered i.v. at doses of 1-2 ng/kg X min in patients with stage II-III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.

AT III activity and concentration were measured in 36 patients (mean age 65.5 yrs, range 43-77 yrs) with ischaemic stroke within maximally 48 h of the acute event. In 12 patients (= 33%) AT III activity was reduced below 18.4 IU/ml: 50% of these patients showed normal and 50% reduced AT III concentration of less than 22 mg/dl. In 15 patients AT III activity and concentration were measured in the acute phase on admission to hospital and 12 months later. In the acute phase, AT III activity was reduced when compared with AT III concentration (y = 0.19 chi + 15.5) and did not correlate with the latter. 12 months later, however, AT III activity and concentration correlated significantly (r = 0.92; p less than 0.001) and the regression line was steeper (y = 0.8 chi). During the acute phase of ischaemic stroke, intravascular coagulation is evidently increased and inactive AT III-thrombin complexes are formed, whereby the concentration of active AT III decreases. A patient with progressive stroke and reduced AT III activity of 14.2 IU/ml was therefore substituted with AT III concentrate. The further neurological course was favourable.

Thirty-seven patients (15 female, 22 male; aged 46–89 years, mean age 68.8 years) with III or IV grade carotid sinus reflex carotid arteries were investigated by sonography (B-scan and CW-Doppler). It was demonstrated that stenoses or arteriosclerotic plaques, localized in the region of the carotid bulb or bifurcation, were present on both sides in 27 patients and on one side only in four patients. Five patients did not show these changes and four of them had thickening of common carotid artery endothelium. Thus, vascular changes occurred in 35 patients. Occlusions and stenoses >50% were visible in five patients. Primarily bilateral changes were shown as well as unilateral and bilateral pathologic reflex response; main localization was the posterior wall of the carotid bulb. Thus, arteriosclerotic changes seem to be important in the development of pathologic carotid sinus reflex. Cerebral complications (left-sided PRIND) occurred in one patient who did not have high degree carotid stenosis. In comparison to other authors who investigated only with CW-Doppler a much higher rate of arteriosclerotic wall changes and a greater occurrence of bilateral changes could be demonstrated by application of the highly sensitive B-scan sonography.

Arterial blood pressure was continuously monitored during rapid atrial pacing in 31 patients with different types of heart disease to determine sinus node recovery time and corrected sinus node recovery time. Pacing was initiated at 70 beats/min and increased stepwise to 160 beats/min. One to one atrioventricular conduction was maintained throughout the one minute stimulation period. Blood pressure fell initially during at least one stimulation period in 21 of our patients and at pacing rates up to 130 beats/min in 18. Once blood pressure had fallen during overdrive pacing maximal sinus node recovery time and maximal corrected sinus node recovery time could not be prolonged by increasing the pacing rate. Sinus node recovery time and corrected sinus node recovery time during the pacing induced fall in blood pressure was significantly shorter than those during stimulation runs with constant blood pressure. No pacing induced fall in blood pressure and no relation between changes in blood pressure and sinus node recovery time were evident in 10 of the 31 patients. Sinus node recovery time is therefore influenced by alterations in autonomic tone due to pacing induced haemodynamic changes.

In adult normothermic cats cerebral blood flow was interrupted for 1 hour by clamping the innominate and subclavian arteries. Following ischemia the brains were recirculated with blood, and the coagulation system was investigated by measuring coagulation times and blood content of fibrinogen and platelets. Ischemia induced progressive consumption coagulopathy with an increase in coagulation times and a decrease of platelets and fibrinogen by more than 40%. Coagulopathy was accompanied by a respiratory distress syndrome with a significant increase in the alveolar-arterial carbon dioxide gradient from --3.3 to --13.5 mm Hg. A correlation was found between plasma fibrinogen concentration, cerebral blood flow and electrophysiological function, indicating that a relationship exists between the severity of postischemic coagulopathy and functional recovery following prolonged cerebral ischemia.

The carotid bifurcations and the common carotid arteries of 36 patients with the diagnosis hyperactive carotid sinus syndrome (HCSS) were investigated by continuous wave (CW) Doppler ultrasonography and high-resolution real-time B-scan. Using these non-invasive tests, the functional impact of luminal stenosis and the morphological changes resulting from arteriosclerotic deformities could be established. Significant differences were found in comparison with a reference group of 199 patients with a high risk of arteriosclerosis. In the HCSS group, 5 patients had a stenosis of more than 50% at the origin of the internal carotid artery on both sides, or on one side in combination with large plaques or a complete occlusion on the contralateral side. Seventy-five per cent of patients in the HCSS group, as compared to only 23.5% of the control group, had effective arteriosclerotic changes in the carotid bifurcation on both sides; 4 patients had such changes only unilaterally. Marked additional bilateral arteriosclerotic depositions were detected in the common carotid arteries of 17 patients (47.2%). In 5 patients no arteriosclerotic lesions were detectable in the carotid bifurcations, but marked changes were found in both common carotid arteries. These data indicate that bilateral arteriosclerotic changes in the carotid bifurcations and/or the common carotid arteries represent an important pathophysiological factor for the development of an HCSS.