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Angiotensin-Converting Enzyme Gene Polymorphism Influences Degree of Left Ventricular Hypertrophy and Its Regression in Patients Undergoing Operation for Aortic Stenosis

Insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in patients with cardiomyopathy and congestive heart failure. Patients with aortic stenosis (AS) have varying degrees of LVH at a given valve area. The aim of this study was to examine the relation between ACE gene polymorphism and the degree of LVH in patients undergoing operation for AS. Eighty-two patients who underwent operation for AS with a stentless valve were followed prospectively with echocardiographic assessments of left ventricular mass index (LVMI). ACE gene polymorphism was determined by polymerase chain reaction. The genotype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aortic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197 +/- 47 g/m2) preoperatively than those with ID (175 +/- 41 g/m2) or II (155 +/- 43 g/m2) genotypes (p = 0.01). LVMI decreased significantly in DD (p <0.001) and ID (p <0.001) genotypes but not in the II genotype during follow-up (mean 15 months). There was a significant difference in regression of LVMI over time between genotypes (p = 0.0056), with no significant difference between genotypes at follow-up. The DD genotype of the ACE gene is associated with increased preoperative LVH in patients treated surgically for AS. The DD genotype appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload.

Circulatory and ventilatory effects of induced platelet aggregation and their inhibition by acetylsalicylic acid.

Protamine chloride was infused into 21 heparinized dogs. After a latency period of 2–6 min from the start of infusion there were falls in the platelet count (‐ 91 %), aortic blood pressure, peripheral vascular resistance and cardiac output. The pulmonary arterial pressure increased (+ 121 %) due to an elevation of the pulmonary vascular resistance (+ 376 %). Simultaneously with the circulatory changes the compliance of the lung decreased (‐ 59 %), the airway resistance increased (+ 99 %) and 1–2 min later there was a fall in arterial oxygen tension (‐ 63 %). Hyperinflation of the lungs restored the compliance and arterial oxygen tension to pre‐infusion values and lowered the pulmonary arterial pressure and vascular resistance. Acetylsalicylic acid injected before protamine did not prevent the falls in platelet count (‐ 93 %) and aortic pressure, but significantly inhibited the increases in pulmonary arterial pressure (+ 28 %) and pulmonary vascular resistance (+ 30 %). The effects of protamine on the airways were also inhibited. The compliance of the lung decreased by only 13 %, the airway resistance increased by 27 % and the arterial oxygen tension decreased by 18 %. There was no inhibition by vagotomy or injection of the serotonin antagonist methysergide before protamine infusion.

Prostacyclin infusion during cardiopulmonary bypass in man

The thrtnabocytopenia and platelet dysfunction often observed during and after cardiopulmonary bypass (CPB) have been thought to contribute to bleeding co!nplications following open heart surgery. Pharmacologic protection of platelets by inhibition of their activation by certain stimuli might diminish blood loss in cardiac surgery provided that the hemostatic function of the platelets is not simultaneously inhibited or at least rapidly reversible following CPB. Prostacyclin seems to fulfill these criteria since it has been shown to protect platelet function and improve hemostasis during and after CPE in dogs (1). The present study (approved by the Ethics carmittee of the Karolinska Hospital) reports on some of our initial experiences with prostacyclin administration during CPB in cardiac surgery patients. The major objective of the study was to find a safe, effective and convenient method of administration of prostacyclin. Preservation of the platelet count during CPB was chosen as the main indicator of the effect of prostacyclin.

Effects of exercise on Doppler-derived pressure difference, valve resistance, and effective orifice area in different aortic valve prostheses of similar size

The effects of increased transvalvular volume flow on Doppler-derived measurements were compared in similarly sized, normally functioning, mechanical prostheses, stented and stentless porcine bioprostheses, and homografts. Homograft and stentless valves showed the largest effective orifice area and the lowest pressure differences and valve resistance at rest and during exercise-induced increase in flow rates.

Mode of Action of Protamine in Regard to Its Circulatory and Respiratory Side Effects

Thirty dogs were subjected to infusions of protamine chloride 30 mg/min. Preceded by a pronounced drop in platelet count, there was 2.5–7 min after the start of the infusion a fall in aortic blood pre

Autotransfusion of mediastinal blood in cardiac surgery

A series of 135 adults undergoing cardiac surgery was randomized to an autotransfusion group (n = 67) or a control group (n = 68). In the autotransfusion group mediastinal blood was collected and reinfused during the first 6 postoperative hours. Blood from the reservoir was taken for bacteriologic culture at the end of that time. The postoperative blood was comparable in the two groups. The average requirement of bank blood was 2.7 units in the autotransfusion group and 3.3 units in the controls (p less than 0.05). The average volume of autotransfusion blood was 336 ml. There were no clinical infections in the autotransfusion group, although 19% of the cultures were positive, and no apparent alteration of the coagulation mechanisms arose from infusion of autologous blood. No clinically significant intergroup differences were found in hematologic, renal or hepatic parameters, neurologic function or use of antibiotics.

Effects of Prostacyclin During Cardiopulmonary Bypass in Man

Effects of prostacyclin infusion were studied in adult patients operated on for acquired heart disease during the period November 1979-June 1980. In group A. 10 patients received prostacyclin 50 ng × kg b.w.−1 x min−1 for the first 30 min of cardiopulmonary bypass (CPB). Twelve patients served as controls. In group B, 14 patients received prostacyclin 100 ng × kg b.w.−1 x min−1 throughout CPB apart from the last 5-20 min. Nine patients served as controls. CPB was by roller pump and bubble oxygenator primed with a crystalloid solution. Hypothermia to 25-28°C was induced. All patients were given heparin 3 mg/kg b.w. before cannulation + 50-75 mg added to the pump prime.There were 3 deaths in the control groups and 1 death in the prostacyclin groups. One control and 2 prostacyclin patients were re-operated on for bleeding. There was no difference between control and prostacyclin patients in regard to intra- or postoperative bleeding. One prostacyclin patient operated on for calcific aortic stenosis suffered ...

Use of the activated coagulation time in cardiac surgery. Effects on heparin-protamine dosages and bleeding.

A standard heparin-protamine protocol was used for a series of 44 patients. In a second series of 82 patients. Activated Clotting Time (ACT) by the Hemochron method was used to control heparinization and its reversal with protamine. The two groups was similar in regard to surgical procedures, pump-times and perfusion technique. Patients in group II controlled by Hemochron received in average 13% less heparin and 48% less protamine than patients in group 1 (p less than 0.001 Students t-test). The intra-operative blood loss was on an average 50% less in group II than in group I (p less than 0.001). There was, however, no significant difference in regard to postoperative bleeding. The introduction of the ACT test thus resulted in reduced dosages of heparin and protamine and in a reduction of intra-operative bleeding, while surgical technique seems to be the main factor in the control of postoperative bleeding.

Influence of Cardiopulmonary Bypass on Some Host Defence Functions in Man

Four different functions of the immune defence were studied in six men undergoing open-heart surgery with cardiopulmonary bypass (CPB). Pre-operatively, a few hours after and three days after surgery the following tests were performed: (I) in vivo phagocytic and metabolic functions of the reticuloendothelial system (RES), (II) haemolytic activity of blood monocytes, (III) nitroblue tetrazolium (NBT) reduction by granulocytes, and (IV) bactericidal capacity of granulocytes. Compared to the pre-operative values, the RES functions were unchanged postoperatively, whereas there was a significant increase in the haemolytic activity of monocytes and in the NBT reduction of granulocytes. The capacity of the granulocytes to kill bacteria was normal a few hours after surgery, but significantly increased on day 3. No infectious complications occurred and all patients recovered uneventfully. These results suggest that, at the present time, open-heart surgery under CPB is accompanied by an increased activity of granulocytes and monocytes in the early postoperative period.

The Effect of Acetylsalicylic Acid on the Peripheral and Pulmonary Vascular Responses to Thrombin

Experiments were made to investigate the nature of the mediating mechanisms in regard to thrombin‐induced pulmonary hypertension in dogs. Infusion of thrombin (200–300 NIH U/min for 2 min) into the right atrium caused platelet aggregation, indicated by a pronounced fall in platelet count, along with a fall in aortic blood pressure and a rise in pulmonary arterial pressure and tracheal insufflation pressure. Injection of acetylsalicylic acid (ASA) before thrombin infusion prevented most of the rise in pulmonary arterial pressure and tracheal insufflation pressure, whereas the fall in platelet count was not inhibited. The increase in femoral blood flow induced by local thrombin infusion (4–10 NIH U/min), previously shown to be mediated by release of adenine nucleotides from platelets, was not inhibited by ASA. It is concluded that ASA inhibited the acute pulmonary reaction to thrombin by some other mechanism than by inhibition of platelet aggregation and release reaction. It is suggested that unidentified smooth muscle active substances, in addition to those secreted in the platelet release reaction, are of major importance for the rise in pulmonary arterial pressure and tracheal pressure induced by thrombin.