Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure.

AIMS: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. METHODS AND RESULTS: Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca2+ handling with more spontaneous Ca2+ release events, increased diastolic Ca2+ , lower Ca2+ amplitude, and prolonged time to diastolic Ca2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (-35%, P < 0.01) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) function (-26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. CONCLUSIONS: Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF.

Pedicled Vein Grafts in Coronary Surgery: Perioperative Data From a Randomized Trial.

BACKGROUND: Less-than-optimal long-term patency of the saphenous vein is one of the main obstacles for the success of coronary artery bypass grafting (CABG). Results from the IMPROVE-CABG trial has shown that harvesting the saphenous vein with a pedicle of perivascular tissue less than 5 mm while using manual distention provides comparable occlusion rates but significantly less intimal hyperplasia at early follow-up. The impact of pedicled veins on duration of operations, leg wound infections, and postoperative bleeding is unknown. METHODS: One hundred patients undergoing first-time elective CABG were randomly assigned to conventional or pedicled vein harvesting. Perioperative and postoperative data were collected prospectively during the hospital stay and at follow-up. RESULTS: Duration of extracorporeal circulation was significantly longer in the pedicled vein group (mean: 76 min versus 65 min, p = 0.006); however, no significant difference was found in the cross-clamp time. No significant difference was found in intraoperative vein graft flow, postoperative bleeding, or leg wound infections (4% in each group). No reoperations were due to vein graft bleeding. CONCLUSIONS: Harvesting a pedicled vein provides comparable postoperative bleeding and leg wound infection rates in selected patients. The technique is associated with a slightly longer duration of extracorporeal circulation than harvesting conventional veins. Promising early results using the pedicled vein technique may contribute to a change in standard vein harvesting technique for CABG in selected patients.

[Thoracic injuries at a regional trauma centre]. / Thoraxskader ved et regionalt traumesenter.

BACKGROUND: The purpose of this study was to establish patient characteristics and the severity and extent of thoracic injury for patients referred to a Norwegian regional trauma centre. MATERIAL AND METHODS: All patients (n = 436) treated for thoracic injuries at St. Olavs University Hospital between 01.01. 2003 and 31.12. 2004 were analysed retrospectively. The patients were identified from the hospital diagnosis registry by ICD-10 codes. RESULTS: Traffic accidents and falls accounted for 92% of all injuries. The most common thoracic injury was rib fracture (55%) and the most common internal thoracic injury was pneumothorax (24%). About half of the patients (221/446) had associated extra-thoracic injuries. Observation and pain relief was the only treatment in 290 patients. Chest tube was the most common treatment, and was used in 88 cases (20%). 50 patients (12%) received ventilator treatment. Nine patients underwent thoracic surgery, four of these died. In-hospital mortality was 5% (20/436 patients). Head injury and bleeding from internal organs were the most frequent causes of death. CONCLUSIONS: Thoracic injuries are a frequent challenge at St. Olavs University Hospital. Many patients have both thoracic and extra-thoracic injuries. Mortality is related to the severity of the injury, advanced age and comorbidity.

Clinical and echocardiographic assessment of the Medtronic Advantage aortic valve prosthesis: the Scandinavian multicentre, prospective study.

OBJECTIVE: The aim of this report is the prospective, multicentre evaluation of clinical results and haemodynamic performance of the Medtronic Advantage aortic valve prosthesis. METHODS: From April 2001 to June 2003, 166 patients (male:female 125:41; mean (SD) age 61.8 (11.8) years) received an aortic advantage valve prosthesis. Complete cumulative follow-up was 242.7 patient-years (maximum 3.2; mean 1.6 years). Postoperatively, patients underwent early (within 30 days) and 1 year transthoracic echocardiography. RESULTS: 30 day mortality was 2.4% (n = 4). Kaplan-Meier estimates of freedom from complications and linearised rates were as follows: 96.9 (1.6)% survival; 94.7 (1.3)% (2.06 patients/year) thrombo-embolism; 99.4 (0.6)% (0.4 patients/year) bleeding; 98.8 (0.9)% (0.8 patients/year) non-structural valve dysfunction; 98.8 (0.9)% (0.8 patients/year) reoperation. Valvular mean pressure gradients ranged from 16 (3) mm Hg for size 19 to 7 (2) mm Hg for size 27 and the corresponding effective orifice areas ranged from 1.2 (0.25) to 3.2 (0.66) cm(2). In all, left ventricular mass significantly decreased (p<0.001) and fractional shortening increased (p<0.001) from postoperative to 1 year echocardiography. CONCLUSIONS: Haemodynamic performance and early clinical results of Medtronic advantage in the aortic position were satisfactory and comparable with those of other bileaflet valves in current clinical use.

Effect of clopidogrel on midterm graft patency following off-pump coronary revascularization surgery.

OBJECTIVE: The aim of the study was to evaluate the effect of clopidogrel on midterm graft patency following off-pump coronary revascularization surgery. DESIGN: Ninety-four consecutive patients who underwent off-pump coronary artery bypass grafting between 1997 and 2002 were studied (58 men, 36 women; 61.7 +/- 9.8 years). The initial 36 patients (control group) received 75 to 160 mg acetyl salicylic acid (ASA) as an antiplatelet agent, whereas the consecutive 58 patients (clopidogrel group) received 75 mg clopidogrel postoperatively in addition to ASA. Intraoperatively, graft flow was assessed with transit-time flowmetry in all patients and the peripheral anastomoses were assessed with epicardial ultrasound in 28 patients. Sixty-two patients underwent angiography after a mean of 185 +/- 92 days. A total of 82 grafts were evaluated angiographically. Grafts with TIMI flow 2 and 3 were assessed as patent. RESULTS: At angiographic follow-up, the overall graft patency rate was 84% (31/37) in the control group and 93% (42/45) in the clopidogrel group (P value was not significant [ns]). Graft patency rates for left internal mammary artery (LIMA) grafts were 92% (23/25) versus 96% (28/29) (ns), and for saphenous vein grafts were 66% (7/11) versus 87% (14/16) (ns), respectively. CONCLUSION: The observed trend toward higher patency rates in patients treated with clopidogrel did not reach statistical significance. Further larger studies are necessary to confirm these preliminary results.

The worldwide mid-term experience with the Medtronic ADVANTAGE bileaflet mechanical heart valve.

BACKGROUND AND AIM OF THE STUDY: A total of 639 patients (479 men, 160 women; mean age 60 +/- 10 years) underwent isolated aortic valve replacement (AVR) between 25 November 1999 and 20 October 2003, using the Medtronic ADVANTAGE bileaflet mechanical heart valve. The study aim was to quantify the clinical performance of a valve with two design modifications: (i) an enlarged central orifice intended to improve blood flow characteristics; and (ii) an asymmetric butterfly pivot recess with expanded outflow component designed to enhance the washing of blood flow through the pivot region. METHODS: Patients were enrolled at 21 centers located in Europe, Canada, Australia, and the USA. The study was conducted under the authority of regional ethics committees, as well as the respective national regulatory agencies. All centers adhered to a common protocol. RESULTS: The total follow up was 1,215.9 patient-years. The average systolic mean pressure gradient across the prosthesis was < 10 mmHg. The mean left ventricular mass index decreased by 22.87 g/m2 (13% reduction) over 12 months. The numbers of valve-related intraoperative, early (< or = 30 days or prior to discharge) and late (> or = 31 days) deaths were 0, 10 and 19, respectively. After one year and four years of follow up, 99.3% (n = 560) and 100% of patients (n = 37), respectively, were in NYHA class I or II. CONCLUSION: The evolutionary bileaflet design of the ADVANTAGE valve achieved the desired clinical functionality and performance.

Bleeding following coronary surgery after preoperative low-molecular-weight heparin.

Low-molecular-weight heparin and acetyl salicylic acid have become an established treatment for unstable angina. A retrospective study on our database of one year was carried out to see what impact preoperative low-molecular-weight heparin versus none had on the postoperative course of 473 patients having coronary surgery exclusively. Apart from the fact that the low-molecular-weight heparin patients had a higher New York Heart Association classification and marginally more grafts, longer bypass and cross-clamp time, the preoperative characteristics and surgery of the two groups were similar. The low-molecular-weight heparin group had twice as many (9.7% versus 4.7%) re-operations for bleeding, 46% versus 26% had blood transfusion and 22.3% versus 12.6% plasma transfusion. The postoperative outcome was otherwise similar. Preoperative treatment of unstable angina with low-molecular-weight heparin carries a definite risk of postoperative bleeding. Although this study did not reveal any serious consequences, bleeding, transfusions and re-operations are associated with infections, wound healing problems and death. The indications and length of treatment with low-molecular-weight heparin in unstable angina patients have to be appropriate and the perioperative management of these patients has to address the bleeding tendency.

Prophylactic treatment with desmopressin does not reduce postoperative bleeding after coronary surgery in patients treated with aspirin before surgery.

UNLABELLED: The synthetic vasopressin analog desmopressin has hemostatic properties and may reduce postoperative bleeding after coronary artery bypass grafting (CABG). A study on the effects of recent aspirin ingestion on platelet function in cardiac surgery showed a greater impairment of platelet function in patients treated with aspirin <2 days before the operation. We evaluated the effects of desmopressin on postoperative bleeding in CABG patients who were treated with aspirin 75 or 160 mg until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel group trial. One-hundred patients were included and divided into two groups. One group received desmopressin 0.3 micro g/kg and the other received placebo (0.9% NaCl) after the neutralization of heparin with protamine sulfate. Postoperative blood loss was recorded for 16 h. The mean (SD) bleeding was 606 (237) mL in the desmopressin group and 601 (301) mL in the placebo group (P = 0.93), representing no significant difference (95% confidence interval, -107 to 117 mL). We conclude that desmopressin does not reduce postoperative bleeding in CABG patients treated with aspirin until the day before surgery. IMPLICATIONS: Continuation of aspirin until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of desmopressin to these patients after the neutralization of heparin with protamine sulfate does not reduce postoperative bleeding.

Marked mixed venous desaturation during early mobilization after aortic valve surgery.

UNLABELLED: We investigated the physiological reaction to mobilization the first and second day after aortic valve replacement in an open, prospective study. Hemodynamic and oxygenation variables were recorded in 15 patients using a pulmonary artery oximetry catheter and bench oximetry. Serious intraoperative events occurred in 3 patients, but all patients began mobilization on the first postoperative day and mobilization was accomplished without clinical problems. Mixed venous oxygen saturation (SvO(2)) at rest was 58.0 +/- 7.7% (mean +/- SD) on the first postoperative day and 58.0 +/- 6.2% on the second day (NS). During mobilization, oxygen consumption increased by 64 +/- 41% and 58 +/- 33% on the first and second days (P < 0.01; NS between days). No compensatory increase in cardiac index and oxygen delivery was seen. Oxygen extraction increased, resulting in SvO(2) values during exercise of 35.7 +/- 6.8% on the first day and 36.7 +/- 7.7% on the second day (P < 0.01; NS between days), whereas mixed venous oxygen partial pressure was 3.0 +/- 0.4 kPa on both days. The lowest recorded value for SvO(2) was 10%. The marked and consistent mixed venous desaturation during early mobilization has not been described before and the clinical consequences and underlying mechanism require further investigation. IMPLICATIONS: During early mobilization after aortic valve replacement, a marked and consistent reduction in mixed venous oxygen saturation to 35% and mixed venous oxygen partial pressure to 3 kPa was observed.

Guiding surgical cannulation of the inferior vena cava with transesophageal echocardiography.

UNLABELLED: We studied 150 adult cardiac surgery patients to assess visualization of the venous cannula and the venous system by intraoperative transesophageal echocardiography and to register the incidence of cannulation of hepatic veins. The quality of images, the dimensions of the venous system, the position of the venous cannula, and the adequacy of venous return were registered. Acceptable image quality of the inferior vena cava and the right hepatic vein (RHV) was obtained in 95% and 87% of cases, respectively. Considerable individual variations were found in the dimensions of the venous system. The cannula position could be determined in 99% of the cases. Ten percent of venous cannulae were primarily placed in the RHV. A short distance between the eustachian valve and the RHV possibly predisposes to cannulation of the RHV. No other patient-related factors were associated with cannula position. Placement of the cannula deep in the inferior vena cava was associated with reduced venous return and may be a more important cause of reduced return than a cannula positioned in a hepatic vein. IMPLICATIONS: Correct positioning of the venous cannula draining blood to the cardiopulmonary bypass circuit is important. Intraoperative transesophageal echocardiography allows satisfactory determination of the cannula position in nearly all patients. Ten percent of venous cannulae are primarily positioned in the right hepatic vein and not in the inferior vena cava as intended.

Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery.

UNLABELLED: Tranexamic acid reduces postoperative bleeding after coronary artery bypass grafting. We evaluated the effects of a single dose of tranexamic acid given immediately before cardiopulmonary bypass (CPB) in patients treated with aspirin until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. Eighty patients were included and divided into two groups: one group received tranexamic acid 30 mg/kg, and one group received placebo (0.9% NaCl) as a bolus injection before CPB. Postoperative blood loss was recorded for 16 h. Transfusions of blood products were recorded for the whole hospital stay. Transfusions of packed red cells were given when the hematocrit value was less than 20% during CPB and less than 25% after surgery. The patients in the tranexamic acid group had significantly less postoperative bleeding compared with the patients in the placebo group (mean [SD]) (475 [274] mL versus 713 [243] mL; P < 0.001). An effective inhibition of fibrinolysis was found in patients receiving tranexamic acid. Tranexamic acid reduces postoperative bleeding in coronary artery bypass grafting patients treated with aspirin until the day before surgery. IMPLICATIONS: Continuation of aspirin medication until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of a single dose of tranexamic acid (30 mg/kg) immediately before cardiopulmonary bypass significantly reduced postoperative bleeding and inhibited fibrinolysis in these patients.

[Coronary surgery--arterial grafts instead of venous grafts?]. / Koronarkirurgi--arteriegraft i stedet for venegraft?

BACKGROUND: Recurrence of symptoms and the need for repeat interventions remains a clinical challenge following coronary artery bypass surgery, despite excellent early results. Saphenous vein graft failure has been identified as a main contributing factor to unsatisfactory long-term results. The use of multiple arterial grafts instead of venous grafts appears to be a promising treatment modality. This article describes our own experience with arterial revascularisation and gives a critical review of the literature. MATERIAL AND METHODS: Extended arterial revascularisation was performed in 30 patients at our institution between 1998 and 2001. Clinical follow-up was performed in all patients; re-angiography was done in six patients. 23 patients were operated on with bilateral mammary arteries; 11 patients received radial artery grafts. RESULTS: The median follow up was 12 months. All patients are alive, none suffered a new myocardial infarction. Our results are in accordance with the published literature. INTERPRETATION: Arterial grafting is a valuable tool in the armamentarium of modern coronary artery bypass surgery. Large randomised trials are required to clarify the role of extended arterial grafting in routine coronary bypass surgery.