Postoperative hemostasis and fibrinolysis in patients undergoing cardiopulmonary bypass with or without aprotinin therapy.

Intra- and postoperative blood loss during open heart surgery is reduced by approximately 50% when aprotinin, a potent inhibitor for plasmin and kallikrein, is administered during surgery. But whether aprotinin increases the risk of thrombotic complications remains controversial. The aim of this study was to evaluate the effects of aprotinin administration on coagulation and fibrinolysis during and after cardiopulmonary bypass (CPB). Thirty patients undergoing CPB were randomly assigned to two comparable groups for a double-blind study (16 patients receiving high-dose aprotinin, 14 patients receiving placebo). Patients' plasma levels of ATM (thrombin-induced modified antithrombin III), FbDP (fibrin degradation products, D-Dimers), t-PA (tissue-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) were measured at regular intervals. In both groups, ATM level increased during surgery (from less than 30 to 90-110 ng/ml) and returned to normal 24 h after surgery and remained unchanged thereafter. Aprotinin reduced this increase in ATM levels (p = 0.02 at 30 min after the start of CPB). The FbDP generated during surgery was greatly reduced in the aprotinin group (945 ng/ml) in comparison with the placebo group (1889 ng/ml, p = 0.004). After surgery, FbDP levels decreased in both groups with nadirs at 2nd day (placebo group: 940 ng/ml and aprotinin group: 865 ng/ml) indicating a hypofibrinolytic period. Then, the FbDP level in both groups started to increase up to the 9th day, in an identical manner.(ABSTRACT TRUNCATED AT 250 WORDS)

An asanguineous reperfusion solution. An effective adjunct to cardioplegic protection in high-risk valve operations.

The protection afforded by cardioplegia during elective ischemic arrest can be partly compromised by a reperfusion injury, which may impede the recovery of cardiac function. We previously showed experimentally that this postischemic damage could be largely avoided by an appropriate crystalloid reperfusate. The present study was thus undertaken to assess the effects of this "reperfusion solution" clinically. One hundred twelve patients undergoing valve replacement with the aid of hypothermic cardioplegia (K+ 12 mEq, Mg2+ 26 mEq) were prospectively divided in two groups: Group I (n = 49) received an unmodified blood reperfusate. In Group II (n = 63), 1 L of the reperfusion solution was delivered just prior to removal of the aortic clamp. The formulation of the reperfusion solution adhered to the following principles: (1) maintenance of cardioplegia (K+ = 15 mEq), (2) replenishment of Ca2+ stores (Ca2+ = 2.5 mEq), (3) substrate provision (glutamate = 2,942 gm), (4) buffering (pH = 7.70 at 28 degrees C), and (5) hyperosmolarity (370 mOsm). The two groups were matched for preoperative data except for a higher incidence of isolated aortic valve replacement (p = 0.01) in Group II. Also, the cross-clamp time (mean +/- standard error of the mean) was longer in Group II (94 +/- 4 minutes versus 63 +/- 4 minutes, p less than 10(-6]. The reperfusion solution was found to increase both the rate and extent of postischemic functional recovery, as evidenced by (1) a lower proportion of catecholamine-supported patients 48 hours after operation (9/63 [14.28%] versus 16/49 [32.6%] in the control group [p less than 0.03]) and (2) a lower amount (gamma/kg/min) of dobutamine required to achieve stable hemodynamics (11 +/- 1 versus 26 +/- 6 in the control group [p less than 0.03]). A similar recovery pattern was noted in the high-risk subgroup of patients with mitral valve disease. Further, serial postoperative hemodynamic measurements were performed in 31 randomly selected patients (10 control and 21 reperfused). Although the reperfused patients were found to be at higher risk because of lower preoperative cardiac indices and longer cross-clamp times, they consistently achieved better postoperative hemodynamics with a lower incidence of catecholamine support. This hemodynamic improvement was particularly reflected by a higher left ventricular stroke work index throughout the postoperative course, the difference being significant 6 hours and 12 hours postoperatively.(ABSTRACT TRUNCATED AT 400 WORDS)

Cancer of the kidney invading the vena cava and heart. Results after 11 years of treatment.

Between October, 1973, and October, 1983, 18 patients with cancer of the kidney or adrenal gland that had invaded the vena cava, and in 11 cases had reached the heart, were operated on by seven surgical teams. The surgical excision in all patients was performed with extracorporeal circulation, circulatory arrest and deep hypothermia. No deaths occurred. If there are no detectable metastases before operation, the 5 year survival rate is 75% as compared to 6 months with medical treatment. This clinical situation is not uncommon, as 3% to 10% of cancers of the kidney invade the inferior vena cava and 40% of them reach the heart. The possibility of curing the cancers with minimal operative risk should prompt a systematic search for venous invasion with any cancer of the kidney.

Simplified method for delivering normothermic blood cardioplegia.

We describe a simple technique for optimizing oxygen delivery during normothermic continuous blood cardioplegia. It involves the use of a minimal volume of cardioplegic agents, the infusion rate of which is adjusted so as to keep the heart arrested. The resulting enhancement of oxygen supply is marshalled from the maintenance of hematocrit values in the range of 0.25.

On-pump, beating-heart coronary artery operations in high-risk patients: an acceptable trade-off?

BACKGROUND: Current cardioplegic techniques do not consistently avoid myocardial ischemic damage in high-risk patients undergoing coronary artery bypass grafting. Alternatively, revascularization without cardiopulmonary bypass is not always technically feasible. We investigated whether an intermediary approach based on maintenance of a beating heart with cardiopulmonary bypass support but without aortic cross-clamping might be an acceptable trade-off. METHODS: Thirty-seven consecutive patients underwent coronary artery bypass grafting (with an average of two grafts per patient) in a pump-supported, non-cross-clamped beating heart. Inclusion criteria were poor left ventricular function (18 patients; mean ejection fraction, 0.25), evolving myocardial ischemia or infarction (11 patients, 5 of whom were in cardiogenic shock), and advanced age (3 patients; mean age 79.5 years) with comorbidities. Results were assessed primarily on the basis of clinical outcome. In addition, measurements of plasma levels of markers of myocardial damage (troponin Ic) and systemic inflammation (interleukin-6, interleukin-10, elastase) were done in 9 patients before and after bypass. In 6 patients, right atrial biopsy specimens were taken before and after bypass and processed by Northern blotting for the expression of messenger ribonucleic acid coding for the cardioprotective heat-shock protein 70. These biologic data were compared with those from control patients who underwent warm cardioplegic arrest within the same time span. RESULTS: There was one cardiac-related death (2.7%), one Q-wave myocardial infarction, and no strokes. Four other deaths occurred from noncardiac causes, yielding an overall mortality rate of 13.5%. Limitation of myocardial injury was demonstrated by the minimal increase in postoperative troponin Ic levels (3.3 +/- 1.0 micrograms/L versus 6.6 +/- 1.5 micrograms/L in controls; p < 0.05) and the finding that heat-shock protein 70 messenger ribonucleic acid levels (expressed as a percentage of an internal standard) were significantly increased after bypass compared with pre-bypass values (279% +/- 80% versus 97% +/- 21%; p < 0.05). In the control group (cardioplegia), end-arrest values of heat-shock protein 70 messenger ribonucleic acid were not significantly changed from baseline (148% +/- 49% versus 91% +/- 29%), a finding suggesting a defective adaptive response to surgical stress. Conversely, peak levels of inflammatory mediators were not significantly different between the two groups. The eight grafts to the left anterior descending coronary artery that were assessed angiographically, by transthoracic Doppler echocardiography, or both methods were patent with satisfactory anastomoses. CONCLUSIONS: In select high-risk patients, on-pump, beating-heart coronary artery bypass grafting may be an acceptable trade-off between conventional cardioplegia and off-pump operations. It is still associated with the potentially detrimental effects of cardiopulmonary bypass but eliminates intraoperative global myocardial ischemia.

Normothermic cardioplegia: is aortic cross-clamping still synonymous with myocardial ischemia?

The enthusiastic clinical reports on normothermic blood cardioplegia contrast with the paucity of data on the myocardial metabolic effects of this technique. The present study was therefore designed to assess whether normothermic blood cardioplegia really provides an aerobic environment during aortic cross-clamping. Thirty-one patients undergoing coronary (16 patients), valve (13 patients), and transplantation (2 patients) procedures were given continuous normothermic blood cardioplegia through the coronary sinus. Myocardial metabolism was assessed either immediately before aortic unclamping (16 patients) by collecting blood simultaneously from the cardioplegia infusion line and the aortic effluent or during reperfusion (15 patients) by collecting blood simultaneously from the radial artery and the coronary sinus. All samples were assayed for markers of anaerobiosis (blood gases, lactates), leukocyte activation (elastase), and lipid peroxidation (malondialdehyde, vitamin E). At the end of arrest, oxygen extraction was low, whereas the production of lactates was small, thereby suggesting the efficacy of normothermic blood cardioplegia in maintaining a predominantly aerobic metabolism. This was confirmed by postarrest data, as oxygen extraction measured immediately after cross-clamp removal was unchanged from prearrest values, whereas lactate metabolism yielded transient and limited production followed by prompt recovery of normal extraction patterns. There was no release of elastase from the myocardium, which suggests adequate protection of the coronary endothelium from ischemic injury and the related increase in leukocyte activation. Likewise, postarrest coronary sinus concentrations of malondialdehyde and vitamin E were identical to the respective arterial concentrations, thereby ruling out the occurrence of intramyocardial lipid peroxidation at the time of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Limitation of vasodilation associated with warm heart operation by a "mini-cardioplegia" delivery technique.

Peripheral vasodilation is commonly seen during and after warm heart operations and can become of clinical concern when it requires vasopressors because some of these drugs adversely affect coronary artery bypass graft flows. As hemodilution lowers systemic vascular resistance, we assessed whether peripheral vasodilation could be limited by a drastic reduction of the volume of infused cardioplegia. Fifty patients underwent isolated coronary artery bypass grafting procedures using normothermic (35 degrees to 37 degrees C) bypass and normothermic continuous retrograde blood cardioplegia. They were divided into two equal groups: in group 1, blood was diluted 4:1 with hyperkalemic crystalloid cardioplegia, whereas in group 2, the cardioplegic "solution" was limited to the sole arresting agents that were concentrated in a small volume (16 mEq potassium chloride and 3 mEq magnesium chloride in a 20-mL ampoule). This "mini-cardioplegia" was continuously added to arterial blood so as to keep the heart arrested. The average volume of cardioplegia per patient was 1,000 mL in group 1 and 58 mL in group 2 (p < 0.0001). The mini-cardioplegia technique resulted in a reduced incidence of perioperative systemic vasodilation: group 2 patients required significantly less vasopressors (p < 0.05) and less volume loading, as reflected by significantly lower right atrial and pulmonary capillary wedge pressures (p < 0.05 and p < 0.03 at 12 hours postoperatively, respectively), compared with group 1 patients who received traditional high-volume cardioplegia. There were no differences between the two groups with respect to myocardial recovery, as assessed by standard clinical and hemodynamic end points.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrograde coronary sinus perfusion: a safe alternative for ensuring cardioplegic delivery in aortic valve surgery.

During aortic valve surgery, cardioplegic solution is delivered through direct cannulation of both coronary ostia. Since this approach may cause an intimal injury leading to acute dissection or late ostial stenosis, we have evaluated retrograde coronary sinus perfusion (RCSP) as a means of delivering cardioplegia in 12 patients undergoing aortic valve replacement. The retroperfusion of the cardioplegic solution was performed with a balloon-tipped catheter inserted into the coronary sinus through the right atrium. The perfusion pressure averaged 40 mm Hg. Twelve patients undergoing antegrade coronary perfusion served as controls. Both groups were matched for preoperative and intraoperative data. The postoperative evaluation focused on hemodynamic status, as evidenced by serial measurements of right-sided pressures and cardiac output at 1, 6, 12, 18, and 24 hours after operation. The stroke volume index and the left ventricular and right ventricular systolic stroke work indexes were then calculated. There was no statistically significant difference between the two groups. We conclude that RCSP is a simple, safe, and effective means of cardioplegic protection during aortic valve surgery.

[Major thrombopenia induced by heparin. Practical approach to cardiac surgery under extracorporeal circulation]. / Thrombopénies majeures induites par l'héparine. Attitude pratique en chirurgie cardiaque sous CEC.

Major heparin-induced thrombocytopaenia (HIT) is a condition which is feared more for its thrombotic complications than for the risk of haemorrhage. The platelet count is part of routine surveillance of patients receiving this treatment which must be withdrawn if HIT occurs. The use of heparin remains essential for cardio-pulmonary bypass surgery. There are two possible scenarios: The thrombocytopaenia occurs in the postoperative period: the standard heparin may be relayed by oral anti-vitamin K anticoagulants, platelet antiaggregant drugs or by low molecular weight heparin (LMWH). The diagnosis of HIT is made before surgery: three therapeutic attitudes are discussed with respect to the urgency of surgery: surgery is deferred for 6 to 8 weeks to allow the platelet count to return to normal and the responsible circulating antibody to disappear; the use of LMWH providing the tests of platelet aggregation are negative with this product; in addition, there are other problems specific to their use in cardiopulmonary bypass to be considered; blood exchange at the beginning of cardiopulmonary bypass to eliminate the circulating factor responsible and so allow the use of standard heparin during and after the operation: this is the only possible solution in cases with in vitro aggregant activity of LMWH.

[Coronary surgery on the beating heart under extracorporeal circulation in high-risk patients. An acceptable compromise?]. / La chirurgie coronaire à coeur battant sous circulation extracorporelle chez les patients à haut risque. Un compromis acceptable?

Coronary artery surgery with cardioplegia in high risk patients carries a risk of myocardial ischaemia and, without cardiopulmonary bypass, is not always technically feasible. The authors assessed an alternative, surgery on the beating heart with haemodynamic assist by cardiopulmonary bypass in 43 consecutive patients with poor left ventricular function (mean ejection fraction: 0.26), evolving myocardial ischaemia or acute myocardial infarction, old age (mean: 79.5 years) and comorbid conditions. Results were assessed mainly on clinical criteria. In addition, 9 patients had pre- and post-cardiopulmonary bypass measurements of markers of myocardial ischaemia (troponine Ic) and systemic inflammation (interleukines 6 and 10, elastase). In 6 cases, right atrial biopsy was analysed for expression of messenger ribonucleic acid coding for heat shock protein (HSP) 70; the data were compared with those of patients operated under warm blood cardioplegia. There was one cardiac death and one myocardial infarction. Myocardial conservation was confirmed by the minimal increase in troponine Ic levels and the significant increase in HSP 70 in RNA suggesting myocardial adaptation to stress. On the other hand, the minimal concentrations of mediators of inflammation were not significantly changed. In selected high risk patients, coronary revascularisation on the beating heart under cardiopulmonary bypass could be a valuable alternative. It conserves the potentially deleterious effects of cardiopulmonary bypass but peroperative global myocardial ischaemia, an important factor in the aggressivity of cardiac surgery, is eliminated.

Blood conservation techniques for cardiac surgery: a survey of French centres.

A survey resulting from a partnership between CECEC (Centre d'Etudes en Circulation Extra-Corporelle) and Laboratoires Hoechst, France was carried out amongst all French adult cardiac surgery centres. The aim of this study was to investigate the various strategies used to decrease blood loss during open-heart surgery. Due to an exceptionally high response rate, we are able to report the current practice of French cardiac centres which account for 75% of open-heart adult surgery. The three most interesting strategies for blood conservation appear to be haemodilution, blood salvage from the extracorporeal circuit and previously deposited autologous blood transfusion, yet the three methods which are predominantly used are haemodilution (92.7%), aprotinin therapy (87.8%) and blood salvage from the extracorporeal circuit (82.9%).

Acute thrombosis of a St. Jude Medical aortic prosthesis in a pregnant woman.

A 24-year-old, 4-months pregnant woman developed an acute thrombosis of a St. Jude Medical aortic valve prosthesis. Upon admission, she was in cardiogenic shock. A thrombectomy was achieved in emergency under cardiopulmonary bypass. The patient survived but not the fetus. Diagnosis, surgical procedure, anticoagulation drugs and valve prostheses in pregnant women are discussed.