Is there a place for preconditioning during cardiac operations in humans?

BACKGROUND: Activation of the kinase cascade (protein kinase C (PKC), tyrosine kinase (TK), and mitogen-activated protein kinase (MAPK) is a key feature of the transduction pathway, elicited by preconditioning signals and mediating their cardioprotective effects. We assessed whether such an activation occurred during cardiac operations and could thus represent a target for cardioprotective strategies. METHODS: A total of 20 patients undergoing coronary artery bypass grafting surgery were studied. During the first 10 minutes of cardiopulmonary bypass (CPB), 10 were treated with sevoflurane (2.5 minimum alveolar concentration), an inhalational anesthetic that mimics preconditioning through a similar activation of the kinase cascade. Ten case-matched patients undergoing 10 minutes of sevoflurane-free CPB served as controls. Right atrial biopsies were taken before and 10 minutes after CPB and were then processed for the measurement of PKC, TK, and p38 MAPK activities by enzyme assay techniques. Troponin I was also monitored over the first 2 postoperative days. RESULTS: Compared with pre-CPB values, PKC and p38 MAPK activities (in nanomoles per milligram of protein per minute and arbitrary units, respectively) increased significantly and to the same extent in both groups: PKC, from 20.7+/-0.7 to 29.9+/-3.9 in controls (p = 0.037) and from 18.4+/-1.1 to 23.9+/-1.8 in sevoflurane (p = 0.016); p38 MAPK, from 88.6+/-8.5 to 312.9+/-66.2 in controls (p = 0.005) and from 114.6+/-14.7 to 213.4+/-51.8 in sevoflurane (p = 0.045). Conversely, sevoflurane triggered a significant increase in TK activity (from 68.5+/-1.4 to 83.7+/-2.9 picomoles per milligram of protein per minute p = 0.0015) which did not occur in controls (from 67.5+/-1.9 to 76.8+/-4.2 picomoles per milligram of protein per minute, p = 0.09). Likewise, the peak postoperative value of troponin I was not different between controls and sevoflurane-treated patients (3.4+/-0.6 vs 2.4+/-0.4, p = 0.21). CONCLUSIONS: Cardiopulmonary bypass triggers an activation of the kinase cascade that is mechanistically linked to opening of potassium channels. The direct opening of these channels by the anesthetic sevoflurane does not increase kinase activation further, nor does it improve markers of cell necrosis, thus suggesting that pharmacologically targeting potassium channels may overlap the preconditioning-like effects of CPB alone.

Cardiac troponin I is an independent predictor of in-hospital death after adult cardiac surgery.

BACKGROUND: Although myocardial injury during cardiac surgery is associated with impaired clinical outcome, little is known about the prognostic value of cardiac troponin I (cTnI), a cardiac-specific biologic marker. The purpose of this prospective study was to evaluate the prognostic value of cTnI concentrations measured 20 h after the end of surgery in adult patients undergoing coronary artery bypass grafting or conventional valve surgery. METHODS: Baseline and perioperative characteristics of 502 consecutive patients undergoing conventional heart surgery during a 1-yr period were collected. In-hospital death (n = 28) and major clinical outcomes, e.g., low cardiac output, ventricular arrhythmia, and renal failure, were recorded. RESULTS: Multivariate analysis, using a stepwise logistic regression, showed that cTnI concentration was an independent predictor of in-hospital mortality (for cTnI concentration > 13 ng/ml, odds ratio = 6.7 [95% confidence interval, 2.3-19.3]), as were diabetes, altered preoperative cardiac function, emergent surgery, cardiopulmonary bypass duration, postoperative Pao2 level and total chest drainage volume. Further, elevated cTnI concentrations were associated with a cardiac cause of death and with major clinical outcomes. CONCLUSIONS: Our results demonstrated that cTnI concentration measured 20 h after the end of surgery is an independent predictor of in-hospital death after cardiac surgery. In addition, elevated concentrations of cTnI are associated with a cardiac cause of death and with major postoperative complications.

Comparison of minithoracotomy and conventional sternotomy approaches for valve surgery.

OBJECTIVE: To compare patients undergoing valve surgery through a minithoracotomy approach with a matched group undergoing conventional valve surgery. DESIGN: Control study. SETTING: University hospital, single center. PARTICIPANTS: Forty-one consecutive patients scheduled for valve surgery by minithoracotomy approach were matched with a similar group of patients operated on by the sternotomy approach. INTERVENTIONS: Criteria for matching included type of valve procedure (aortic valve replacement or mitral valve repair), age, surgeons, and left ventricular function. Two surgeons performed the surgical procedures. Perioperative care was standardized for all patients. Operative and postoperative data were recorded. MEASUREMENTS AND MAIN RESULTS: The 41 pairs of patients were correctly matched, except for left ventricular function (n = 1). Twenty patients underwent mitral valve repair and 62 aortic valve replacement. Preoperative demographic data and clinical characteristics were similar in both groups. Cardiopulmonary bypass, aortic clamping, and surgery times were longer in the minithoracotomy group (p < 0.05). In 3 patients, the minithoracotomy approach had to be converted into a sternotomy during the surgical procedure for better visualization. Minithoracotomy patients had significantly increased postoperative total blood loss (p < 0.05). No difference was found between the groups for extubation time and intensive care or in-hospital lengths of stay. CONCLUSION: These results suggest that valve surgery is feasible in many cases through minithoracotomy. Nevertheless, this approach increases surgical complexity and in this comparative study no significant benefit was shown.

Renal dysfunction after cardiac surgery with normothermic cardiopulmonary bypass: incidence, risk factors, and effect on clinical outcome.

UNLABELLED: Renal dysfunction is a frequent and severe complication after conventional hypothermic cardiac surgery. Little is known about this complication when cardiopulmonary bypass (CPB) is performed under normothermic conditions (e.g., more than 36 degrees C). Thus, we prospectively studied 649 consecutive patients undergoing coronary artery bypass surgery or valve surgery with normothermic CPB. The association between renal dysfunction (defined as a > or =30% preoperative-to-maximum postoperative increase in serum creatinine level) and perioperative variables was studied by univariate and multivariate analysis. Renal dysfunction occurred in 17% of the patients. Twenty-one (3.2%) patients required dialysis. Independent preoperative predictors of this complication were: advanced age, ASA class >3, active infective endocarditis, radiocontrast agent administration <48 h before surgery, and combined surgery. When all the variables were entered, active infective endocarditis, radiocontrast agent administration, postoperative low cardiac output, and postoperative bleeding were independently associated with renal dysfunction. The in-hospital mortality rate was 27.5% when this complication occurred (versus 1.6%; P < 0.0001). Furthermore, postoperative renal dysfunction was independently associated with in-hospital mortality (odds ratio, 4.1 [95% confidence interval, 1.3-12.8]). We conclude that advanced age, active endocarditis, and recent (within 48 h) radiocontrast agent administration, as well as postoperative hemodynamic dysfunction, are more consistently predictive of postoperative renal dysfunction than CPB factors. IMPLICATIONS: We found that postoperative renal dysfunction was a frequent and severe complication after normothermic cardiac surgery, independently associated with poor outcome. Independent predictors of this complication were advanced age, active endocarditis, and recent (within 48 h) radiocontrast agent administration (the only preoperative modifiable factor), as well as postoperative hemodynamic dysfunction.