Effects of the combinations propofol/alfentanil and midazolam/fentanyl on blood pressure and contact phase system during coronary surgery.

Perioperative haemodynamic changes leading to severe circulatory problems during open-heart surgery still represent dreaded complications. The aim of this study was to examine the relationship between the use of applied anaesthetic agents and alterations of the contact phase of the intrinsic blood-clotting system, as changes within the kallikrein-kinin system can lead to a fall in blood pressure. In a randomized study, parameters of the kallikrein-kinin system, coagulation and fibrinolysis were determined for 36 patients with aortocoronary bypass operations. The patients had been given either midazolam/fentanyl or propofol/alfentanil to maintain anaesthesia. Perioperative blood pressure values were registered at seven fixed points. The measured values of the factor XIIa-like activity and the kallikrein-like activity suggested a higher activation of the contact phase, when propofol/alfentanil was given. From the start of the extracorporeal circulation (ECC) to the end of the operation, the kallikrein-like activities in the propofol/alfentanil group were significantly higher than those of the midazolam/fentanyl group. Also, the results of the kallikrein inhibition capacity and the indicators of fibrinolysis (t-PA and D-dimers) indicate a stronger activation of the contact phase--at least at the beginning of recirculation--and as a result of it, a stronger fibrinolysis within the propofol/alfentanil group. In addition, the hypotensive side-effects differed significantly between the two groups. Patients receiving propofol/alfentanil needed the triple amount of antihypotonicum to maintain the mean arterial blood pressure above 75 mmHg. With the results of this study, a correlation between the application of propofol/alfentanil, contact phase activation, with activation of the kallikrein-kinin-bradykinin system and the observed hypotension, can be presumed.

[Arterial dominance of the hand]. / Arterielle Dominanz der Hand.

Arterial dominance in the hand was studied in 164 hands using digital pulse electronic oscillography (DPEO) and the Allen test. It was seen that the radial artery more frequently delivered the main blood supply to the digits (radial-ulnar dominance 12.8: 4.2%). The situation where no collateral circulation is present deserves special attention (absolute dominance). This was observed in 3% of the cases for the radial and in 1.2% for the ulnar artery. The Allen test was found useful in detecting ulnar artery dominance for the radial artery, however, false negative results may be obtained. In addition, 29 hands with a thrombosed radial artery were studied. No collateral circulation other than from the ulnar artery could be demonstrated. Since dominance of the ulnar artery is less common and can be reliably assessed with the Allen test, a forearm flap based on the ulnar artery appears to be safer than a radial forearm flap.

Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage.

Nowadays in many European heart centers the activation of the fibrinolytic system, always occurring during cardiopulmonary bypass, is routinely reduced by high-dose application of the proteinase inhibitor aprotinin (total of > 4 million KIU). In this study parameters of myocardial ischemic injury were investigated with the aim of identifying further benefits of aprotinin, particularly the protection of the myocardium during the ischemic period of aortic crossclamping. Forty patients with coronary artery disease who underwent aorta-coronary bypass grafting were randomly and in a double-blind fashion divided into two groups, one that received high-dose aprotinin therapy and one that received only saline solution. Markers such as troponin T, with high specificity for detection of myocardial ischemia and infarction, and markers with more general specificity such as creatine kinase, its isoenzyme, and lactate dehydrogenase showed significantly increased values after ischemia in both groups. In patients who received high-dose aprotinin therapy 3 days after cardiopulmonary bypass all parameters measured showed significantly lower levels compared with those in the control group. Therefore we can presume that the application of high-dose aprotinin provides myocardial protection from perioperative ischemic injury.

Heparin-coated oxygenators significantly reduce contact system activation in an in vitro cardiopulmonary bypass model.

Over the past decade our group has shown that the contact system of blood is activated in cardiopulmonary bypass (CPB), that heparins enhance this activation and that aprotinin reduces both this activation and blood loss in CPB. We have developed an in vitro CPB model to assess the effects of added components to blood and new components in the artificial devices of CPB. In the present study we have compared membrane oxygenators with or without heparin-coated surfaces under identical conditions in the CPB model. Recalcified ACD blood was circulated in a closed system for 90 min at 28 degrees C. Blood samples were taken at various times during circulation. 4 IU/ml heparin was used with the non-coated oxygenators; no heparin was used in the coated system. Heparin levels were measured in the plasma together with various contact system components. Haemolysis, platelet count, platelet factor 4 and alpha 1-proteinase inhibitor-PMN elastase complexes, were also determined. No heparin was detected during the period of recirculation in samples from the coated oxygenators, showing the excellent adhesive quality of the heparin coating. In keeping with a significant greater fall in the platelet count in non-coated vs coated oxygenators (mean [+/- SD] final counts of 170 +/- 50 x 10(9)/l and 97 +/- 34.2 x 10(9)/l respectively after 90 min circulation), platelet factor 4 levels were significantly higher (682.9 +/- 187.3% and 95.8 +/- 46.5% of the initial value respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The prolonged activated clotting time (ACT) with aprotinin depends on the type of activator used for measurement.

In cardiopulmonary bypass (CPB) surgery high dose heparin is necessary to inhibit the clotting cascade which is activated through damage to the vessels (extrinsic pathway) as well as contact activation of the blood with the various artificial surfaces of the CPB machine (intrinsic pathway). In most European heart surgery centres, the fibrinolytic activation that always occurs in CPB due to contact activation is reduced by the proteinase inhibitor aprotinin. Monitoring of anticoagulation during CPB is performed with the activated whole blood clotting time (ACT). The two machines commonly used for this purpose, Hemotec and Hemochron, use different contact system activators, kaolin and celite. These activators displayed highly significant differences, in both in vitro tests (modified APTT with whole blood in a neutral coagulometer), and ACT in both machines where aprotinin and heparin were used, as well as with parallel measurements with the two machines with blood from patients undergoing CPB with high dose aprotinin therapy (P < 0.001). The Hemotec machine with kaolin as activator was not affected by aprotinin throughout surgery, while the Hemochron clotting times almost doubled as soon as aprotinin and heparin were combined. Our studies show that for the determination of ACT in CPB were high dose aprotinin therapy is used only ACT determinations with machines using kaolin as activator yield accurate results.

Aprotinin in cardiopulmonary bypass--effects on the Hageman factor (FXII)--Kallikrein system and blood loss.

Aprotinin has been used in our hospital in open heart surgery for almost 20 years and recently published studies have revealed a reduction in postoperative blood loss under this therapy. In the present study patients undergoing aorto-coronary bypass operations received either 20,000 KIU aprotinin/kg body weight (group 2) or 60,000 KIU aprotinin/kg body weight (group 3). Another group of patients without aprotinin served as a control (group 1) and postoperative bleeding was more pronounced in these patients compared with the other groups. In parallel, slight reductions in kallikrein-like activity were observed in patients treated with aprotinin. Furthermore, we have shown that the main inhibitor of the contact phase, C1-esterase-inhibitor, loses some of its activity against beta-FXIIa in the presence of heparin. Aprotinin was able to partly antagonize this phenomenon. All studies dealing with the effect of aprotinin in extracorporeal circulation demonstrate hyperfibrinolysis in untreated patients. Aprotinin is known to inhibit plasmin at low concentrations and thus reduced the postoperative bleeding tendency (group 2). In addition, plasma kallikrein is inhibited by high aprotinin concentrations and is responsible for a reduced activation of the contact phase system. This effect led to a further reduction in blood loss (group 3).

The effects of fractionated and unfractionated heparins with and without aprotinin on plasma inhibition of alpha and beta FX11a.

Chromogenic peptide substrate assays were used to compare the effects of fractionated and unfractionated heparins on plasma inhibition of alpha and beta FX11a, with and without various concentrations of aprotinin. All of the heparins reduced beta FX11a inhibition at 1 or 2U/ml. Four heparins increased alpha FX11a inhibition. Aprotinin counteracted the reduction in beta FX11a inhibition and augmented the heparin potentiation of alpha FX11a inhibition.

Studies on components of the plasma kallikrein system as a risk factor in diabetics undergoing cardiopulmonary bypass.

Components of the FX11-kallikrein systems were determined in blood samples from non diabetics and diabetics undergoing cardiopulmonary bypass (CPB). FX11 and prekallikrein levels fell in both groups with the largest falls in the diabetic group. Kallikrein inhibition was also lower in the diabetic group. Alpha-2-macroglobulin levels were lower in the diabetic group before operation and were markedly lower throughout CPB. Kallikrein like activities were also lower in the diabetic group. Beta FX11a inhibition values were higher in the diabetic group and fell in both groups during CPB. From the results obtained we concluded that the lower levels of FX11, prekallikrein, kallikrein inhibition and alpha-2-macroglobulin in the diabetic patients during CPB reflect enhanced activation of the FX11-plasma kallikrein systems. Blood loss in the diabetic group was higher than the for non diabetic group.

Laser angioplasty of peripheral arterial occlusive disease.

To evaluate the impact of laser ablation of arteriosclerotic material on the long-term results of transluminal angioplasty, 103 patients were treated by laser-assisted recanalization of peripheral arterial occlusion and followed-up for 6 and 12 months. Two pulsed laser systems (308 nm-excimer laser and 504 nm-dye laser) were tested. Laser energy was transmitted via wire-guided 4.5-, 7- and 9-French multifiber catheters. Stand-alone laser angioplasty was possible in 22% of the patients, especially in the popliteal and the lower-limb arteries. Compared to the results of balloon dilatation in the literature, the clinical success rate at 6 and 12 months after the treatment was better in occlusions with a length between 6 and 10 cm, however no improvement was seen in either shorter or longer occlusion. Due to the limited size of percutaneously applicable catheters, laser treatment and pretreatment seemed to be of most benefit in distal femoropopliteal arteries and in lower-limb arteries. Clinical improvement after revascularization depends on a sufficient run-off in branching vessels distal to the recanalized artery segment.

Early and late results of the modified Waterston shunt with PTFE grafts for palliation of complex congenital cyanotic heart disease in neonates.

During a 12 year period from 1978 to 1989, 35 infants under 4 weeks of age underwent palliative surgery for complex congenital cyanotic heart disease with a short (1-1.5 cm) PTFE graft between the ascending aorta and the right pulmonary artery (modified Waterston shunt). Twenty-three infants had pulmonary atresia and 14 had severe pulmonary stenosis. Underlying cardiac lesions were tetralogy of Fallot (n = 11), single ventricle (n = 7), transposition complexes (n = 6), and intact ventricular septum and hypoplastic right heart syndrome (n = 13). There were 4 early deaths (10.7%) in the entire series, 2 of which were shunt related. Three of the 4 occurred during our initial experience with this shunt in 1978 and 1979. They led to the modified Waterston shunt being abandoned for 3 years in favor of other shunt procedures. Since 1983 one early death occurred in 28 infants (3.5% mortality) with no death in the latest 26 patients. All patients were followed up between 6 and 108 months. There were 4 late deaths, one of which was shunt related. We observed a significant difference in the shunt patency rate between 4 and 5 mm grafts: palliation was adequate after 2 years in 52% of the patients when a 4 mm graft was used and in 89% of the 5 mm graft group (p less than 0.005). Reshunting was necessary in 7 infants between 5 and 60 months after primary surgery. Recatheterization was performed in 17 infants for suspected shunt failure (n = 6) or diagnostic reasons (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

FXII.

The plasma protein FXII (Hageman factor) has been shown to be linked with the plasma defence systems of coagulation, fibrinolysis, kallikrein-kinin and complement. It can be activated by surface contact activation and in solution. Surface contact activation is a complex phenomenon involving negatively charged surfaces, FXII, high molecular weight kininogen and plasma kallikrein. Fluid-phase activation can be effected by a variety of serine proteases. In both types of activation the FXII zymogen is converted to active enzymes. FXII levels in plasma are low or undetectable in both inherited deficiencies and in a variety of clinical conditions. FXII levels can also be elevated in some clinical conditions. Although discovered as a clotting protein FXII appears to play an important role in the kallikrein-kinin and fibrinolytic systems and also has effects on cells. Recent studies suggest that therapeutic blockade of activation of FXII can be of benefit in certain clinical conditions.

[Results of emergency aortocoronary venous bypass surgery after failed percutaneous transluminal coronary angioplasty in patients with unstable angina pectoris]. / Ergebnisse der notfallmässigen aorto-koronaren Venen-Bypass-Operation nach fehlgeschlagener perkutaner transluminaler Koronarangioplastie bei Patienten mit instabiler Angina pectoris.

During a 4-year period from January 1985 to December 1988 140 patients underwent percutaneous transluminal coronary angioplasty (PTCA) of the culprit-vessel for unstable angina. Seventeen patients (12%) needed emergency aorta coronary bypass surgery (ACVB) for failed angioplasty. In 15 cases the culprit-vessel was the LAD and in 2 cases a dominant right coronary artery. Only in 2 cases a history of myocardial infarction was present. Twelve patients were in hemodynamic stable condition after arriving in the operating-room. Five patients were hemodynamic unstable, 4 of them were in cardiogenic shock. Four patients died representing an operative mortality rate of 23%. Three patients died from pump failure despite intraaortic balloon counterpulsation in 2 cases. One patient died from cerebral damage 12 day after surgery. All patients who died were in cardiogenic shock preoperatively. Two patients who survived suffered an extensive myocardial infarction. Thus including the patients who died from pump failure the perioperative infarction rate was 30%. From these results it is concluded that emergency ACVB after failed PTCA of the culprit-vessel in patients with unstable angina results in a significant higher mortality and morbidity as compared with patients who had primary surgery for unstable angina. The prognosis of patients after failed PTCA for unstable angina depends on the hemodynamic situation thereafter and becomes worse in patients with cardiogenic shock.

Pulmonary hypertensive vasculopathy--no indication for corrective operation of isolated ventricular septum defect in babyhood.

The frequency of surgical closure of a ventricular septum defect (VSD) in the first year of life has risen from 10% to 30% in the last seven years in West Germany. Whereas there was a decrease of mortality in older children, mortality has stagnated at 8% for correction at age 12 months or less (early correction). Development of an irreversible pulmonary hypertensive vasculopathy (PHVP) and recurrent heart failure with growth disorders are given as reasons for operation in the first year of life. In the last six years, we have operated on 31 infants for isolated VSD with pulmonary hypertension (PH) and closed the VSD. In approximately equal preoperative pressure in the two ventricles with a pressure ratio of 0.88 +/- 0.16, there was an immediate fall in pressure in the right ventricle with pressure ratios of 0.43 +/- 0.24. Three patients (9.7%) died perioperatively. In the same period, a primary VSD closure was carried out in 120 children even after over 12 months with three deaths (2.5%). Pulmonary tissue removed in this operation did not show any PHVP in four patients (13%), grades 0 to I and I to II in 10 patients each (total 33%) and a PHVP grade II to III in six patients (20%). This PHVP is capable of full regression. An irreversible PHVP does not develop up to the end of the first year of life in isolated VSD with PH, so that the correction can be safely postponed to the beginning of the second year of life provided that recurrent heart failure with growth disorders does not compel earlier correction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Asymptomatic carotid stenosis: is surgical prevention of infarct still justified?]. / Asymptomatische Karotisstenose: ist die operative Insultprophylaxe noch gerechtfertigt?

The present retrospective study compared the incidence of TIA, stroke, and death in patients with asymptomatic carotid stenosis (greater than 50%) during a follow-up period of 24 to 30 months. 65 patients were operated and 193 treated medically. The incidence of death was comparable in both groups. Death in most patients was due to cardiac disease or cancer. The annual incidence of TIA and stroke was not different between the two populations. Despite the low incidence of perioperative complications (%) surgery of asymptomatic carotid stenosis cannot be recommended at the present time.

Alterations in electrolyte and trace-element concentrations during simulated extracorporeal blood circulation.

In our studies with simulated extracorporeal blood circulation we observed damaging effects on blood cells, especially under oxygenating conditions. In order to characterize these effects we also analysed electrolyte and trace-element concentrations in plasma during and after simulated extracorporeal blood circulation. Highest resorption effects for magnesium and highest desorption effects for calcium, copper and iron are found with oxygen gas flow in the system. Membrane permeability for electrolytes seems to be induced as well. Cellular damage due only to mechanical stress within the perfusion system can be neglected.