A randomized study of coronary artery bypass surgery performed with the Resting Heart™ System utilizing a low vs a standard dosage of heparin.

OBJECTIVES: Allogeneic blood transfusion and reoperation for postoperative bleeding after the coronary artery bypass grafting have a negative impact on the patient outcome. This study aimed at evaluating the effects of reduced doses of heparin and protamine on the patient outcome, using a heparin-coated mini-cardiopulmonary bypass (CPB) system. METHODS: Sixty patients undergoing elective first-time CPB were prospectively randomized either to have a reduced systemic heparinization [activated clotting time (ACT) = 250 s] or to a control group perfused with a full heparin dose (ACT = 420 s). Blood transfusions, ventilation time, early postoperative bleeding, ICU stay, reoperations for bleeding, postoperative cognitive status and the level of mobilization were registered. RESULTS: Twenty-nine patients were randomized to the control group, 27 patients to the low-dose group and 4 patients were excluded because of protocol violations. Four patients in the control group received a total of 10 units of packed red blood cells, and in the low-dose group, no transfusions were given, P = 0.046. No patient was reoperated because of bleeding. The ICU stay was significantly shorter in the low-dose group (8.4 vs 13.7 h, P = 0.020), less dependent on oxygen on the first postoperative day (78 vs 97%, P = 0.034), better mobilized (89 vs 59%, P = 0.006) and had less pain (visual analogue scale 2.0 vs 3.5, P = 0.019) compared with the control group. CONCLUSIONS: The use of a mini-CPB system combined with a low dose of heparin reduced the need for blood transfusions and may facilitate the faster mobilization of the patients.

The Scandinavian multicenter hemodynamic evaluation of the SJM Regent aortic valve.

BACKGROUND: 112 patients who received small and medium sized St. Jude Regent heart valves (19-25 mm) at 7 Scandinavian centers were studied between January 2003 and February 2005 to obtain non-invasive data regarding the hemodynamic performance at rest and during Dobutamine stress echocardiography (DSE) testing one year after surgery. MATERIAL AND METHODS: 46 woman and 66 men, aged 61.8 ± 9.7 (18-75) years, were operated on for aortic regurgitation (17), stenosis (65), or mixed dysfunction (30). Valve sizes were 19 mm (6), 21 mm (33), 23 mm (41), 25 mm (30). Two patients receiving size 27 valves were excluded from the hemodynamic evaluation. Pledgets were used in 100 patients, everted mattress in 66 and simple interrupted sutures in 21. Valve orientation varied and was dependent on the surgeons' choice. 34 patients (30.4%) underwent concomitant coronary artery surgery. RESULTS: There were two early deaths (1.8%) and three late deaths, one because of pancreatic cancer. Late events during follow-up were: non structural dysfunction (1), bleeding (2), thromboembolism (2). At one year follow up 93% of the patients were in NYHA classes 1-2 versus 47.8% preoperatively. Dobutamine stress echocardiography (DSE) was performed in a total of 66 and maximal peak stress was reached in 61 patients. During DSE testing, the following statistically significant changes took place: Heart rate increased by 73.0%, cardiac output by 85.5%, left ventriclular ejection fraction by 19.6%, and maximal mean prosthetic transvalvular gradient by 133.8%, whereas the effective orifice area index did not change. Left ventricular mass fell during one year from 215 ± 63 to 197 ± 62 g (p < 0.05). CONCLUSION: The Dobutamine test induces a substantial stress, well suitable for echocardiographic assessment of prosthesis valve function and can be performed in the majority of the patients. The changes in pressure gradients add to the hemodynamic characteristics of the various valve sizes. In our patients the St. Jude Regent valve performed satisfactory at rest and under pharmacological stress situation.

Circulating particles during cardiac surgery.

Shed blood is known to be a source of lipid micro-emboli in cardiac surgery. The aim of this study was to characterize the occurrence of these particles at different stages of the operation, and to study their occurrence in the circulation at multiple time-points after the retransfusion of shed blood. Forty-four patients undergoing routine surgery with cardiopulmonary bypass were included. Blood was sampled from the surgical field at different sampling locations during the operation. Shed blood was collected in a transfusion bag and retransfused. After which, blood was sampled from the arterial line of the heart-lung machine. A Coulter counter was used for particle determinion. The mean volume of shed blood collected was 340+/-215 ml. Particles in the size range 10-60 microm were found at varying concentrations, with the highest concentrations being found in blood collected after cannulation and from the pleura. After retransfusion of this blood, a biphasic response was seen in the blood drawn from the efferent line of the heart-lung machine. Particles are found in shed blood at all times during cardiac surgery, and when this blood was retransfused an increase was seen in particle concentration in the heart-lung machine.

Pressure transduction to the thoracic cavity during topical negative pressure therapy of a sternotomy wound.

The present study was performed to examine pressure transduction to the thoracic cavity during topical negative pressure (TNP) therapy of a sternotomy wound. Seven pigs underwent median sternotomy. Pressure transduction catheters were placed on the anterior surface of the heart (under the foam), in the pericardium (under the heart), in the left pleura and in the oesophagus at the level of the heart. The wound was sealed as for TNP therapy. The vacuum source was set to deliver negative pressures between -50 and -200 mmHg. The pressure on the anterior surface of the heart changed in a linear relationship with the applied negative pressure and was slightly lower than the applied negative pressure (-102 +/- 9 mmHg at delivered -125 mmHg). Further down in the thoracic cavity, in the pericardium (under the heart), in the left pleura and in the oesophagus, the wound pressure was only slightly affected by TNP therapy. In conclusion during TNP therapy, negative pressure is effectively transmitted to anterior portions of the heart. This may explain our recent findings that TNP increases microvascular blood flow in the myocardium. The pressure difference between the anterior and the posterior portions of the heart causes the right ventricle to be sucked up towards the posterior parts of the sternum, where it might be exposed to the sharp edges of the sternal bone, which may result in heart injury.

Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways.

BACKGROUND: Up-regulation of vascular endothelin type B (ETB) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, ex vivo, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ETB receptors in human internal mammary arteries. METHODS: Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using in vitro pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ETA and ETB receptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists. RESULTS: The endothelin-1-induced contraction (after endothelin ETB receptor desensitization) and the endothelin ETA receptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ETB receptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 microM bisindolylmaleimide I and 10 microM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 microM SB203580, 10 microM PD98059 and 10 microM SP600125, respectively). CONCLUSION: In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ETB receptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ETB receptor changes in cardiovascular disease.

A compare between myocardial topical negative pressure levels of -25 mmHg and -50 mmHg in a porcine model.

BACKGROUND: Topical negative pressure (TNP), widely used in wound therapy, is known to stimulate wound edge blood flow, granulation tissue formation, angiogenesis, and revascularization. We have previously shown that application of a TNP of -50 mmHg to the myocardium significantly increases microvascular blood flow in the underlying tissue. We have also shown that a myocardial TNP levels between -75 mmHg and -150 mmHg do not induce microvascular blood flow changes in the underlying myocardium. The present study was designed to elucidate the difference between -25 mmHg and -50 mmHg TNP on microvascular flow in normal and ischemic myocardium. METHODS: Six pigs underwent median sternotomy. The microvascular blood flow in the myocardium was recorded before and after the application of TNP using laser Doppler flowmetry. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium), and after 20 minutes of LAD occlusion (ischemic myocardium). RESULTS: A TNP of -25 mmHg significantly increased microvascular blood flow in both normal (from 263.3 +/- 62.8 PU before, to 380.0 +/- 80.6 PU after TNP application, * p = 0.03) and ischemic myocardium (from 58.8 +/- 17.7 PU before, to 85.8 +/- 20.9 PU after TNP application, * p = 0.04). A TNP of -50 mmHg also significantly increased microvascular blood flow in both normal (from 174.2 +/- 20.8 PU before, to 240.0 +/- 34.4 PU after TNP application, * p = 0.02) and ischemic myocardium (from 44.5 +/- 14.0 PU before, to 106.2 +/- 26.6 PU after TNP application, ** p = 0.01). CONCLUSION: Topical negative pressure of -25 mmHg and -50 mmHg both induced a significant increase in microvascular blood flow in normal and in ischemic myocardium. The increase in microvascular blood flow was larger when using -25 mmHg on normal myocardium, and was larger when using -50 mmHg on ischemic myocardium; however these differences were not statistically significant.

Endothelin receptor-mediated vasodilatation: effects of organ culture.

Culture of intact arteries is a frequently employed experimental model for investigating the mechanisms governing the regulation of vascular endothelin receptors. Endothelin type A (ET(A)) and type B (ET(B)) receptors on vascular smooth muscle cells are up-regulated in organ culture and the enhanced vasoconstriction mimics the changes that occur in cardiovascular disease. The effect of organ culture on endothelial dilatory endothelin ET(B) receptors is not known. We hypothesize that organ culture decreases the endothelin receptor-mediated dilatation and that this is one possible mechanism by which the effects of the endothelin in blood vessels are altered during culture. Porcine coronary arteries were studied before and after 24 h of culture, using in vitro pharmacology and immunofluorescence. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ET(A) and ET(B) receptor effects, and the antagonists, Nomega-nitro-l-arginine (l-NOARG) for nitric oxide (NO), indomethacin for prostaglandins and charybdotoxin in combination with apamin for endothelium-derived hyperpolarizing factor (EDHF), were used to study the endothelium-derived dilatory mediators. Organ culture induced up-regulation of the sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1 (ET(A) receptor agonist) elicited vasoconstriction. The sarafotoxin 6c contraction was stronger after endothelium denudation, suggesting endothelium-dependent dilatation. The endothelin-1 contraction was not affected by endothelium denudation. The increase in sarafotoxin 6c contraction after removal of the endothelium was more pronounced before than after organ culture, suggesting down-regulated endothelial endothelin ET(B) receptors. Also, the immunofluorescence staining intensities for endothelial endothelin ET(B) receptors were higher before than after organ culture. Pre-incubation with inhibitors for dilatory mediators suggested that both NO and EDHF play a vasodilatory role, while prostaglandins are not involved. In conclusion, endothelial endothelin ET(B) receptors induce NO and EDHF mediated vasodilatation in porcine coronary arteries. In organ culture, endothelial endothelin ET(B) receptors are down-regulated, mimicking the changes that occur in cardiovascular disease. Down-regulation of endothelial endothelin ET(B) receptors may in part explain the increased endothelin ET(B) receptor-mediated vasoconstriction frequently studied in organ culture.