Impact of postoperative blood pressure control on regression of left ventricular mass following valve replacement for aortic stenosis

Objective: Considerable left ventricular (LV) hypertrophy sometimes remains after aortic valve replacement (AVR) for aortic stenosis. For this issue, most previous studies have focused solely on transprosthetic pressure gradient, although true problem is not the pressure gradient itself but an elevated LV pressure. This study investigated the impact of blood pressure on postoperative LV mass regression, which had been overlooked in previous studies. Methods: Seventy-nine adult patients with pure aortic stenosis who were treated with AVR using bileaflet mechanical valves underwent echocardiography before surgery, around 6 months later (‘early’), and 2–3 years later (31.7±14.7 months, ‘late’). Patients were divided into two groups whether postoperative systolic blood pressure was below (n=47; N group) or above 130 mmHg (n=32; H group) following recommendation of WHO-ISH and JNC 7th report. Preoperative LV mass (g/m²) did not differ significantly (232±80 vs. 243±76, P=0.91). Results: LV mass became significantly smaller and regression was significantly more effective in N group than in H group both at ‘early’ (145±43 vs. 180±54, regression against preoperative value 34.6±19.1 vs. 19.9±26.6%, P=0.007) and ‘late’ (132±41 vs. 178±51, regression 41.1±16.0 vs. 21.0±27.0%, P<0.001) evaluations. Regression between ‘early’ and ‘late’ evaluations was significant only in N group (P=0.012). The LV mass index returned to the normal range at ‘late’ evaluation in 52.1% of N group and 12.5% of H group patients (P<0.001), and 25 out of 29 patients without residual LV hypertrophy were N group patients. Multivariate analyses revealed that preoperative LV mass index (P<0.001) and postoperative systolic blood pressure (P=0.007) showed significant influence on postoperative LV mass index, and postoperative systolic blood pressure alone significantly (P<0.001) influenced the regression ratio of the LV mass against the preoperative value. No prosthesis related variables (size, orifice area index, pressure gradient) had significant influence. Conclusions: For LV mass regression after AVR, postoperative blood pressure appeared to be more important than prosthesis selection. Controlling the systolic blood pressure below 130 mmHg was beneficial, which coincided with recommendation of WHO-ISH and JNC 7th report despite the pressure drop due to prosthesis in the aortic position.     

Does sodium nitroprusside reduce lung injury under cardiopulmonary bypass?

Objective: We hypothesized that direct pulmonary arterial infusion of sodium nitroprusside (SNP) would ameliorate lung injury under cardiopulmonary bypass. Methods: Experiments were performed on 12 adult mongrel dogs of both sexes weighing 20–28 kg. The animals were randomly divided into two groups of six animals each. All animals were subjected to total cardiopulmonary bypass (CPB) and moderate hypothermia (28°C core temperature). During total CPB, the aorta was clamped together with the pulmonary artery to prevent any antegrade flow to the lungs. After cardioplegic arrest for 120 min, the animals were rewarmed, weaned from CPB, and their condition stabilized for another 90 min. After the release of the aortic cross-clamp, the dogs received either a 5% glucose solution as a placebo (group I) or SNP (0.5 μg/kg per min) (group II), both infused into the pulmonary arterial line. The infusion was stopped after 60 min. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes count, lung tissue samples were taken before CPB and after weaning from CPB. In addition, alveolar-arterial oxygen difference (AaDO₂) for tissue oxygenation was calculated by obtaining arterial blood gas samples. Results: Values of MDA before CPB of 42.0±5.3 nmol/g of tissue rose to 67.6±5.7 nmol/g of tissue after weaning from CPB in group I (P=0.028). In group II MDA values also increased from 43.1±4.3 to 52.4±5.7 nmol MDA/g of tissue after weaning from CPB (P=0.046). The MDA increase in group II after CPB was found to be significantly lower than that for group I (P=0.004). The wet-to-dry lung weight ratio in the sodium nitroprusside group was 5.1±0.2, significantly lower than in the control group (6.8±0.4), (P=0.01). AaDO₂ increased significantly in group I (P=0.028). There was no statistically significant difference (P=0.065) between groups I and II. During histopathological examination it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups. The increase in group I was significantly larger than that in group II (P<0.001). Conclusions: The results represented in our study indicate that pulmonary arterial infusion of sodium nitroprusside during reperfusion can reduce lung injury under cardiopulmonary bypass.     

Residual fibrosis affects a long-term result of left ventricular volume reduction surgery for dilated cardiomyopathy in a rat experimental study

Objectives: The aim of this study is to evaluate the relationship between left ventricular (LV) wall property and the results of LV volume reduction surgery (LVR) to treat dilated cardiomyopathy (DCM) in an experimental model. Methods: DCM was introduced in 18 Lewis rats by autoimmunization with cardiac myosin. Among them, 12 rats underwent LVR and the rest were served as controls. They were subjected to echocardiography and cardiac catheterization for dimensional and functional measurements. The animals were sacrificed 4 weeks after surgery, and the fraction of myocardial fibrosis was calculated in 4 divided parts of the LV wall. Results: Percent fibrosis varied widely from 4.7 to 45.2%. LV volume reduction surgery improved cardiac function immediately after surgery in all rats (E_max, 0.28±0.14 to 0.48±0.18 mmHg/μl; LV end-diastolic pressure, 21.0±6.1 to 13.3±5.1 mmHg, P<0.05, respectively). Four weeks later, 6 hearts remained in good shape with smaller LV end-diastolic dimension (Dd) than baseline values (LV Dd, 9.7±0.6 mm; fractional area change (FAC), 40.3±8.4%) and the other 6 had more redilation in diameter and more deterioration in function than baseline values (LV Dd, 10.9±0.6 mm; FAC, 25.8±6.9%; P<0.05, respectively). Percent fibrosis in the septum differed 11.1±3.4 vs. 27.8±2.8% between the two groups (P<0.01). There was a significant correlation between the ratio of LV redilatation after surgery and percent fibrosis in the septum (r=0.951, P<0.01). Conclusions: Although the initial benefit of LVR was confirmed, the long-term result was affected by the amount of residual fibrosis. This information suggests that surgical site selection is important to achieve a good result of LV restoration surgery for DCM.     

Pyruvate/dichloroacetate supply during reperfusion accelerates recovery of cardiac energetics and improves mechanical function following cardioplegic arrest

Objectives: Cardioplegic arrest during cardiac surgery induces severe abnormalities of the pyruvate metabolism, which may affect functional recovery of the heart. We aimed to evaluate the effect of pyruvate and dichloroacetate administration during reperfusion on recovery of mechanical function and energy metabolism in the heart subjected to prolonged cardioplegic arrest. Methods: Four groups of rat hearts perfused in working mode were subjected to cardioplegic arrest (St. Thomas’ No. 1), 4 h of ischaemia at 8°C and reperfusion with either Krebs buffer alone (C) or with 2.8 mM pyruvate (P), with 1 mM dichloroacetate (D), or with a combination of both (PD). Mechanical function was recorded before cardioplegic arrest and at the end of experiments. In groups C and PD, additional experiments were performed using ³¹P nuclear magnetic resonance spectroscopy in non-working Langendorff mode to evaluate cardiac high-energy phosphate concentration changes throughout the experiment. Results: Improved recovery of cardiac output (% of the preischaemic value±SEM, n=9–12) was observed in all three treated groups (65.7±4.3, 59.5±5.2 and 59.5±5.3% in PD, P and D, respectively) as compared with C (42.2±4.6%; P<0.05). Recovery of coronary flow was improved from 66.4±3.8 in C to 94.9±8.6% in PD (P<0.05). The phosphocreatine recovery rate in the first minutes of reperfusion was increased from 9.9±1.5 in C to 31.5±4.3 μmol/min per g dry wt in PD (P<0.001). No differences were observed in ATP or phosphocreatine concentrations at the end of experiment. Conclusions: The administration of pyruvate and dichloroacetate improves the recovery of mechanical function following hypothermic ischaemia. Accelerated restoration of the energy equilibrium in the initial phase of reperfusion may underlie the metabolic mechanism of this effect.     

Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass

Objective: In coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) the inflammatory response is suggested to be minimized. Coronary anastomoses are performed during temporary coronary occlusion. Inflammatory response and myocardial ischaemia need to be studied in a randomized study comparing CABG in multivessel disease with versus without CPB. Methods: Following randomization 30 consecutive patients received CABG either with (n=16) or without CPB (n=14). Primary study endpoints were parameters of the inflammatory response (interleukin (IL)-6, interleukin-10, ICAM-1, P-selectin) and of myocardial injury (myoglobin, creatine kinase-MB (CK-MB), troponin I) (intraoperatively, 4, 8, 16, 24 and 48 h after surgery). The secondary endpoint was clinical outcome. Results: The incidence of major (death: CABG with CPB n=1, not significant (n.s.)) and minor adverse events (wound infection: with CPB n=2, without CPB n=1, n.s.; atrial fibrillation: with CPB n=3, without CPB n=2, n.s.) was comparable between both groups. The release of IL-6 was comparable during 8 h of observation (n.s.). Immediately postoperatively IL-10 levels were higher in the operated group with CPB (211.7±181.9 ng/ml) than in operated patients without CPB (104.6±40.3 ng/ml, P=0.0017). Thereafter no differences were found between both groups. A similar pattern of release was observed in serial measures of ICAM-1 and P-selectin, with no difference between both study groups (n.s.). Eight hours postoperatively the cumulative release of myoglobin was lower in operated patients without CPB (1829.7±1374.5 μg/l) than in operated patients with CPB (4469.8±4525.7 μg/l, P=0.0152). Troponin I release was 300.7±470.5 μg/l (48 h postoperatively) in patients without CPB and 552.9±527.8 μg/l (P=0.0213). CK-MB mass release was 323.5±221.2 μg/l (24 h postoperatively) in operated patients without CPB and 1030.4±1410.3 μg/l in operated patients with CPB (P=0.0003). Conclusions: This prospective randomized study suggests that in low-risk patients the impact of surgical access on inflammatory response may mimic the influence of long cross-clamp and perfusion times on inflammatory response. Our findings indicate that multiregional warm ischaemia, caused by snaring of the diseased coronary artery, causes considerably less myocardial injury than global cold ischaemia induced by cardioplegic cardiac arrest.     

Downsizing of the mitral valve and coronary revascularization in severe ischemic mitral regurgitation results in reverse left ventricular and left atrial remodeling

Objective: Data of combined mitral downsizing by restrictive prosthetic ring annuloplasty and coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy and moderately severe to severe mitral regurgitation (MR) are rare, and little is known about the effect on reverse left ventricular (LV) and left atrial (LA) remodeling. Methods: Thirty-eight patients (70.6±8.3 years) with coronary artery disease, ischemic cardiomyopathy (LV ejection fraction [LVEF] 31±8%) and moderately severe to severe MR (grade 3.6±0.5) underwent CABG and mitral downsizing by 2–4 ring sizes. Clinical follow-up and serial transthoracic echocardiographic studies were performed after surgery (discharge, 3±0.5 months, 13±7 months) to assess survival, NYHA class, MR, leaflet coaptation height, LA and LV dimensions/volumes, fractional shortening (FS) and LVEF. Results: Early mortality (<30 days) was 2.6%, survival at follow-up was 92 and 85%, respectively. NYHA class improved from 3.3±0.6 to 1.5±0.6 (P<0.001). Residual MR at discharge and at follow-up was grade 0.5 and 0.6, respectively (P<0.001). Leaflet coaptation height was 8±1 mm and did not change over time. LV end-diastolic, end-systolic and LA dimensions decreased from 60±7 to 57±8 mm, from 47±9 to 42±9 mm and from 51±5 to 45±4 mm, FS increased from 23±9 to 28±10% (P<0.001); LV end-diastolic and end-systolic volumes decreased from 188±33 to 171±30 ml and from 129±35 to 105±33 ml, LVEF increased from 31±8 to 39±10% (P<0.001). Conclusions: Combined mitral downsizing and CABG surgery was performed with excellent clinical results: only minimal residual MR, a significant reduction of LA dimension and an increase of LV contractility due to reverse remodeling were observed.     

Aortic valve replacement in severe aortic stenosis with left ventricular dysfunction: determinants of cardiac mortality and ventricular function recovery

Objective: The influence of left ventricular (LV) dysfunction on survival of patients with severe aortic stenosis is poorly characterized. Few data are available about preoperative predictors of cardiac mortality and LV function recovery after aortic valve replacement of such patients. The aim of our study was to examine the outcome and the preoperative predictors of postoperative cardiac death and of LV function recovery in these patients. Methods: We evaluated 85 consecutive patients with severe aortic stenosis (aortic valve area <1 cm²) and severe depression of LV ejection fraction (EF) <35% at cardiac catheterization. Among them, 52 underwent aortic valve replacement and they were compared to patients who were not operated on. All patients had a mean clinical follow-up of 53 months and 94% of them had a mean echocardiographic follow-up of 14 months after aortic valve replacement. Results: The mean baseline characteristics included: LVEF 28±6%, peak-to-peak transvalvular gradient 51±29 mmHg, aortic valve area 0.63±0.25 cm². Thirty-three patients did not undergo aortic valve replacement: 32 of them died within 3 years. Fifty-two patients underwent aortic valve replacement and 16 had a concomitant coronary bypass surgery. In-hospital mortality was 8%. Postoperative NYHA functional class changed from 2.84±0.67 to 1.43±0.44 (P<0.001) and LVEF from 29±6% to 43±10% (P<0.001). At follow-up 10 patients died of heart disease. By multivariate analysis, preoperative LV end-systolic volume index (ESVI) was the only covariate of cardiac death (LVESVI/10 ml/m², OR 1.3, CI 1.1–1.8, P<0.028). By using a receiver operating characteristic curve, LVESVI≤90 ml/m² was the best cut-off value (sensitivity and specificity 78%) to fit with a better survival (93% vs. 63%, P<0.01) and with LVEF recovery after aortic valve replacement (EF improved by 15±10% vs. 8±5%, P<0.001). Conclusions: Despite LV dysfunction, aortic valve replacement appears to change drastically the natural history of severe aortic stenosis. Preoperative LV levels predict different postoperative survival rate and LVEF recovery.     

Pulmonary lactate release following cardiopulmonary bypass

Objective: The etiology of lung injury following cardiopulmonary bypass (CPB) is multifactorial. Our study focused on quantifying the lactate release from the lungs precipitated by extracorporeal circulation at different time points after the insult. This was complemented by an evaluation of the gas exchange at the level of the alveolar–capillary membrane. Methods: Forty consecutive patients (age 61 ± 11 years, EuroScore 4.7 ± 2.7) undergoing CABG were prospectively analyzed. The data are presented as medians and the interquartile range. Results: The pulmonary lactate release (PLR) increased from a baseline value of 0.033 (range −0.077 to 0.170) to 0.465 mmol/min/m² (range 0.113–0.922), which was seen 6 h postoperatively (P < 0.001). The A-a O₂ gradient increased from 12.7 (range 8.8–15) to 39.1 kPa (range 30.3–46.5) upon discontinuation of CPB (P < 0.001). The systemic arterial lactate (L_S) concentration increased from 1.22 (range 1–1.44) to 3.03 mmol/l (range 2.29–4.76) 6 h after surgery (P < 0.001). The veno-arterial pCO₂ difference (V-A dpCO₂) rose from 0.6 (range 0.5–0.9) to 0.9 kPa (range 0.7–1) (P = 0.014). The mortality in the studied group was 5% (2/40). Conclusions: The lungs were found to be a significant source of lactate, and this pulmonary lactate flux was accentuated by CPB. The PLR correlated with systemic hyperlactatemia as well as the A-a O₂ gradient, and was found to be higher in patients requiring prolonged mechanical ventilatory support. The duration of CPB had a significant impact on the systemic lactate concentrations, V-A dpCO₂ and the A-a O₂ gradient, but not on the PLR.     

Preemptive analgesia with controlled-release oxycodone is successful in prevention of post-inguinal herniorrhaphy pain

In a double-blind randomized study, controlled-release (CR) oxycodone (OxyContin ®) administration was assessed against placebo to ascertain the extent of postinguinal herniorrhaphy pain control. Patients received a single dose of CR oxycodone (40 mg orally) or placebo 40 min before surgery.

When post-surgical pain was first reported, a visual analogue scale (VAS) was used to assess pain score. Postoperative pain-free time, dolestin (opiod) and dipyrone (antipyretic) consumption were assessed 24 h after the surgery. Postoperative pain-free time in the CR oxycodone group (Group I) was 655±548 min versus 112±71.5 min in the placebo group (Group II) (P<0.02). Postoperative 24 h dolestin consumption was 8.3±19.5 mg (Group I) versus 120.1±89.2 mg (P=0.004) (Group II). Postoperative 24 h dipyrone consumption in Group I was 0.58±0.67 g versus 1.42±1.0 g in Group II (P=0.004). Accordingly, 41.7% of patients in Group I demonstrated a need for postoperative analgesic drugs was versus 100% of the patients in Group II (P=0.037). Conclusions: Preemptive administration of a single 40 mg oral dose of CR oxycodone significantly reduced both postoperative pain and consumption of analgesic agents, without causing side effects, and may be useful in an ambulatory surgery setting.     

Depressed Function in Remote Myocardium After Myocardial Infarction: Influence of Orotic Acid

Background. We have previously shown that infarction impairs recovery of global function after subsequent cardioplegic arrest and that therapy with orotic acid improves recovery. The aim of this study was to measure the effect of infarction on regional and global left ventricular function and to determine whether orotic acid exerts a beneficial effect exclusive of the effects of cardioplegia.

Methods. Acute myocardial infarction was produced in dogs. They then received either orotic acid or placebo (control) orally (n = 12 per group). Fractional radial shortening and systolic wall thickening were measured by two-dimensional echocardiography before and 1 and 3 days after infarction with and without β-adrenergic blockade, and in 6 dogs up to 9 days after infarction. Global function was measured under anesthesia 4 days after infarction.

Results. In control animals, fractional radial shortening in the infarct decreased from 20.6% ± 5.1% before infarction to 3.0% ± 2.2% at day 1 and to 1.9% ± 1.9% at day 3 (p < 0.01). In the border zone radial shortening declined from 21.9% ± 3.7% to 11.0% ± 2.3% at day 1 and 9.3% ± 2.8% at day 3 (p < 0.05). In the noninfarcted myocardium radial shortening also declined from 27.1% ± 1.9% before infarction to 18.3% ± 2.3% on day 1 (p < 0.05) and to 16.0% ± 2.8% on day 3 after infarction (p < 0.05) with recovery to preinfarct levels by 9 days after infarction. These findings were confirmed by measurements of systolic thickening. Before infarction β-receptor blockade decreased fractional shortening in all regions of the left ventricle, but this effect was absent on day 3 after infarction, implying that the myocardium had become less responsive to β-adrenergic stimulation. Measurements of global function 4 days after infarction showed marked depression of stroke work. There was no effect of orotic acid treatment on regional or global function.

Conclusions. Myocardial infarction causes reversible depression of resting function and β-adrenergic responsiveness in the remote and border zone areas, which is not prevented by metabolic therapy with orotic acid. This finding may explain the adverse response of the infarcted heart to cardioplegic arrest.

(Ann Thorac Surg 1996;62:1765–72)     

Heparin-Bonded Circuits Decrease Myocardial Ischemic Damage: An Experimental Study

Background. Heparin-bonded cardiopulmonary bypass circuits reduce complement activation, but their effect on myocardial function is unknown. This study was undertaken to determine whether heparin-bonded circuits reduce myocardial damage during acute surgical revascularization.

Methods. In 16 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, all animals were placed on percutaneous bypass followed by standard cardiopulmonary bypass during the periods of cardioplegic arrest and reperfusion. In 8 pigs, heparin-bonded circuits were used, whereas 8 other pigs received nonbonded circuits.

Results. Animals treated with heparin-bonded circuits had the best preservation of wall motion scores (3.5 ± 0.3 versus 2.3 ± 0.2; 4 = normal to −1 = dyskinesis; p < 0.05), least tissue acidosis (change in pH = −0.31 ± 0.02 versus −0.64 ± 0.08; p < 0.05), smallest increase in lung H₂O (1.7% ± 0.7% versus 6.1% ± .5%; p < 0.05), and the lowest area of necrosis/area of risk (20.3% ± 2.2% versus 40.4% ± 1.6%; p < 0.05).

Conclusions. We conclude that heparin-bonded circuits significantly decrease myocardial ischemic damage during acute surgical revascularization.     

Dose dependent effects of cardiac beta2 adrenoceptor gene therapy

BACKGROUND: Adenoviral-mediated gene transfer during cardiopulmonary bypass (CPB) achieves efficient myocardial transgene expression. The optimal vector dose required to produce not only increased beta adrenoceptor (betaAR) density but, more importantly, enhanced left ventricular (LV) function is unknown. In addition, it is unclear if absent extracardiac expression in preliminary studies represented cardiac specific, as opposed to selective gene delivery, as a consequence of low vector doses. MATERIALS AND METHODS: Adenoviral vector encoding the human beta(2) adrenoceptor (Adeno-beta(2)AR) was delivered to cardioplegic arrested hearts of neonatal piglets during CPB in three doses ranging from 5 x 10(11) total viral particles (tvp) to 2 x 10(12) tvp. Control animals received adenoviral vector encoding beta galactosidase (Adeno-betagal) or PBS (PBS). LV and liver betaAR density and in vivo LV function were assessed 5 days later. RESULTS: Elevated LV betaAR density was present after delivery of Adeno-beta(2)AR at all doses. Piglets which received 5 x 10(11) tvp and 1 x 10(12) tvp Adeno-beta(2)AR demonstrated enhanced LV dP/dt(max) but in those receiving 2 x 10(12) tvp LV dP/dt(max) was unchanged. Moreover, at this higher dose of adenoviral vector the detrimental effects of cardiac inflammation and extracardiac gene overexpression became apparent. CONCLUSIONS: Although the highest increase in cardiac betaAR density occurred after high-dose Adeno-beta(2)AR, LV dP/dt(max) was not enhanced. Moreover, significant extracardiac gene expression was present at this dose, emphasizing the need for careful dose response studies in gene therapy. However, cardiac selective beta(2)AR overexpression does occur following adenoviral vector delivery during CPB and cardioplegic arrest resulting in enhanced LV dP/dt(max).     

Prospective randomized trial of single clamp technique versus intermittent ischaemic arrest: myocardial and neurological outcome

Objective: To explore the hypothesis that intermittent ischaemic arrest (IIA) provides better myocardial preservation but generates a larger number of cerebral microemboli (ME) and consequently a higher incidence of post-operative cerebral dysfunction compared with the single clamp technique (SCT). Methods: Ninety-one patients with stable angina undergoing elective CABG with no clinical evidence of aortic or cerebro-vascular or neurological disease were prospectively randomized to: IIA (n=43) or SCT with intermittent anterograde cold blood cardioplegia (n=48). Myocardial preservation was assessed by measuring serum CK-MB, Troponin-T (TnT) and Troponin-I (TnI) and from pre- and post-operative ECGs and left ventricular (LV) function by echocardiography. Intra-operative cerebral ME were counted by transcranial Doppler of the right middle cerebral artery. All patients completed the Luria Nebraska Neuropsychological Battery (LNNB) tests for motor, visual, reading, memory and intellectual processes the day before surgery and at 1 week and 6 months post-operatively. Serum levels of the neuro-specific protein S-100 were measured. Results: The two groups were comparable for age, sex, extent of coronary disease, previous myocardial infarction, diabetes, hypertension and number of arterial and venous grafts. The median number of ME detected per patient was 34 (range 4–208) and was similar in both groups. Protein S-100 levels remained normal and similar in both groups at all times except in one patient with SCT who had an operative stroke. LNNB scores were similarly depressed at 1 week and recovered in all cases at 6 months. There was no correlation between the number of ME and LNNB scores. Median peak TnI levels were 0.64 μg/l with IIA vs. 0.87 μg/l with SCT (P=NS) and TnT 0.8 μg/l vs. 1.08 μg/l (P<0.03). SCT was however associated with longer mean ischaemic (67.6±16.1 vs. 34.5±16.5 min, P<0.001) and mean bypass time (88.5±18.2 vs. 74.6±26.3min, P<0.004) than IIA. Four patients with SCT and none with IIA had ECG changes suggestive of MI (P=0.04). Conclusion: During elective CABG in patients with no clinical evidence of aortic or cerebro-vascular disease the incidence of peri-operative ME and post-operative neuropsychological disturbances are comparable with both techniques of myocardial preservation. Biochemical analysis suggests that IIA provides more effective myocardial preservation.     

Evaluation of preoperative intra-aortic balloon pump support in high risk coronary patients

Objective: The intra-aortic balloon pump (IABP) is an established additional support to pharmacological treatment of the failing heart after myocardial infarction, unstable angina and cardiac surgery. The effect of preoperative IABP in high risk patients was evaluated. Methods: Between June 1994 and March 1996 all high risk patients for CABG (two or more of these criteria: Left ventricular ejection fraction (LVEF) ≤40%, left main stem stenosis ≥70%, REDO-CABG, unstable angina) were randomized into either of 3 groups: (1) IABP 1 day prior to surgery, (2) IABP 1–2 h prior to CPB and (3) no preoperative IABP, controls. Exclusion criteria: cardiogenic shock preoperatively. Fifty-two patients have entered the study—group 1 (13 patients), group 2 (19 patients) and group 3 (20 patients). Preoperative patient characteristics and operative data revealed no group differences. There were 56% REDO's, unstable angina 59%, LVEF≤40%, 87% (34.0±11.6%) and left main stem stenosis in 35%. Results: The CPB-time was shorter in groups 1 and 2 88.7±20.3 min than in group 3 105.5±26.8 min, P<0.001, while ischemia time did not differ. Hospital mortality was higher in group 3, 25% vs. 6% (groups 1 and 2). Postoperative low cardiac output was seen in 12 patients (60%) in group 3 vs. 6 patients (19%) in groups 1 and 2, P<0.05. Cardiac index increased significantly prior to CPB in groups 1 and 2. After CPB cardiac index was significantly higher in groups 1 and 2 compared to Group 3 and continued to increase. The IABP was removed after 3.1±1.0 days in group 3 vs. 1.3±0.6 days in groups 1 and 2, P<0.001. In group 3, 11 patients required IABP postoperatively compared to only 4 patients in groups 1 and 2. ICU stay was shorter in groups 1 and 2—2.3±0.9 days vs. 3.5±1.1 days for group 3, P=0.004. All patients received dopamin postoperatively, however in a lower dose in groups 1 and 2, 4.5 vs. 13.5 μg/kg/min. Dobutamine was added in 23% of the patients (group 1), 32% (group 2) and 95% (group 3). Adrenalin/amrinonum was required in 40% of the patients in group 3, 5% in group 2 and none in group 1. Group 1 patients had a better improvement of cardiac performance than group 2, while other parameters did not differ. Three months follow up of hospital survivors showed no group differences. Conclusions: The use of preoperative IABP in high risk patients lowers hospital mortality and shortens the stay in ICU, due to improved cardiac performance, compared to a controls. The procedure was cost-beneficial. One day preoperative IABP treatment improves cardiac performance more than 1–2 h preoperative IABP treatment, but does not significantly affect the outcome in terms of hospital mortality or postoperative morbidity.     

Continuous monitoring of myocardial acid–base status during intermittent warm blood cardioplegia

Objective: Intermittent warm blood cardioplegia (IWBC) is a well-established technique for myocardial protection during cardiac operations. According to standardized protocols, IWBC administration is currently performed every 15–20 min regardless of any individual variable and in the absence of any instrumental monitoring. We devised a new system for continuous measurement of the acid–base status of coronary sinus blood for on-line evaluation of myocardial oxygenation during IWBC. Methods: In 19 patients undergoing cardiac surgery for coronary artery bypass graft and/or valve surgery and receiving IWBC (34–37°C) by antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every 15 min, continuous monitoring of myocardial oxygenation and acid/base status was performed by means of a multiparameter PO₂, PCO₂, pH, and temperature sensor (Paratrend7 ®, Philips Medical System) inserted into the coronary sinus. Results: Mean cross-clamping time was 76±26 min; ischemic time was 13±0.2 min. pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. After every ischemic period, the pH adaptation curve showed a complex pattern reaching step-by-step lower minimum levels (7.28±0.14 during the first ischemic period, to 7.16±0.19 during the third ischemic period – P=0.003). PO₂ decreased rapidly at 90% in 5.0±1.2 min after every reperfusion. During ischemia, PCO₂ increased steadily at 1.6±0.1 mmHg per minute, with progressively incomplete removal after successive reperfusion, and progressive increase of maximal level (42±12 mmHg during the first ischemic period, to 53±23 mmHg during the third ischemic period – P=0.05). Conclusions: Myocardial oxygen, carbon dioxide, and pH show marked changes after repeated IWBC. Myocardial ischemia is not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO₂ and pH after each reperfusion. Progressive increase of reperfusion durations or direct monitoring of myocardial oxygenation could be advisable in cases of prolonged cross-clamping time.     

Bradykinin protects the rabbit heart after cardioplegic ischemia via NO-dependent pathways

Background. Depressed myocardial performance is an important clinical problem after open heart surgery. We hypothesized pretreating with bradykinin would pharmacologically precondition the heart and improve postischemic performance, and induce myocardial preconditioning by activating nitric oxide synthase.

Methods. Thirty-three rabbit hearts underwent retrograde perfusion with Krebs-Henseleit buffer (KHB) followed by 50 minutes of 37°C cardioplegic ischemia with St. Thomas’ cardioplegia solution (StTCP). Ten control hearts received no pretreatment. Ten bradykinin-pretreated hearts received a 10-minute infusion of 0.1 μMol/L bradykinin-enriched KHB and cardioplegic arrest with 0.1 μMol/L bradykinin-enriched StTCP. Six other hearts received 0.1 μMol/L HOE 140, a selective B2 receptor antagonist, added to both the 0.1 μMol/L bradykinin-enriched KHB and 0.1 μMol/L bradykinin-enriched StTCP solutions. Finally, six other hearts received 100 μMol/L of N-Ω-nitro- -arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, added to both the 0.1 μMol/L bradykinin-enriched KHB and 0.1 μMol/L bradykinin-enriched StTCP solutions.

Results. Bradykinin pretreatment significantly improved postischemic performance and coronary flow (CF) compared with control (LVDP: 53 ± 5* vs 27 ± 4 mm Hg; +dP/dt_max: 1,025 ± 93* vs 507 ± 85 mm Hg/s; CF: 31 ± 3* vs 22 ± 2 mL/min; *p < 0.05). Both HOE 140 and L-NAME abolished bradykinin-induced protection, resulting in recovery equivalent to untreated controls.

Conclusions. Bradykinin pretreatment improves recovery of ventricular and coronary vascular function via nitric oxide-dependent mechanisms. Pharmacologic preconditioning by bradykinin pretreatment may be an important new strategy for improving myocardial protection during heart surgery.     

Pre- and postoperative exercise capacity associated with hemodynamics in adult patients with atrial septal defect: A retrospective study

Objective: This study evaluated the pre- and postoperative exercise capacity in adult patients with atrial septal defect (ASD) associated with hemodynamic variables. Methods: Adults (70) with ASD underwent symptom-limited exercise tests. Peak O₂ uptake (Peak VO₂) and % peak VO₂, that is the percentage of predicted value, were measured. These patients were divided into three groups according to pulmonary-to-systemic flow ratio (Qp/Qs) and systolic pulmonary arterial pressure (PAs); Group A: Qp/Qs3, PAs50 mm Hg, Group B: Qp/Qs>3, any PAs, Group C: Qp/Qs3, PAs>50 mm Hg. Exercise test was repeated in 22 patients after surgical closure of ASD (mean 4.6±2.0 months). Results: Peak VO₂ was significantly lower in group B (P<0.01) and group C (P<0.01) than in group A (19.3±5.7, 17.6±3.6, 27.6±6.3 ml/min/kg, respectively). In patients except those in group C, there were a weak negative correlation between PAs and % peak VO₂ (r=0.61) and a significant negative correlation between Qp/Qs and % peak VO₂ (r=0.86). Postoperative peak VO₂ increased significantly in group A (27.2±5.1–31.1±5.1 ml/min/kg, P<0.05) and group B (16.7±3.3–21.5±2.1 ml/min/kg, P<0.01). However, there was no significant difference between pre- and postoperafive peak VO₂ in group C (16.8±1.3–17.8±2.8 ml/min/kg, NS). Conclusions: In ASD patients except those with small or moderate left-to-right shunt and high pulmonary arterial pressure, there was a significant negative correlafion between Qp/Qs and peak VO₂ corrected by age and gender. Patients with large left-to-right shunt and/or high pulmonary arterial pressure had reduced exercise capacity. However, exercise capacity in patients with large left-to-right shunt increased after closure of ASD regardless of whether they had high pulmonary arterial pressure.     

The role of Na/H exchange in the efficacy of multidose hypothermic cardioplegia in immature rabbit hearts

Objectives: Recent studies have demonstrated that the use of a Na⁺/H⁺ exchange inhibitor as an additive can enhance the cardioprotective efficacy of cardioplegia in the adult heart under both normothermic and hypothermic conditions. However, few references are available as to the cardioprotective effect of acidic cardioplegia or Na⁺/H⁺ exchange inhibitors in the neonatal heart, particularly under hypothermic conditions. Methods and results: In isolated working hearts from rabbits aged 7–10 days, function was assessed prior to 10 h of ischemia (20 °C) and again after 35 min of reperfusion. All hearts received a pre-ischemic infusion (10 ml) of cardioplegic solution (20 °C) at pH 7.8, followed by nine subsequent infusions (5 ml every 1 h) of cardioplegic solution (20 °C) at pH 6.6, 7.0, 7.4, 7.8 (control) or 8.2 (n=8/group). When the pH was increased to 8.2, post-ischemic recovery of cardiac output was reduced and cumulative creatine kinase (CK) leakage during cardioplegic infusions was increased. In contrast, when the pH of the cardioplegic solution was lowered to 6.6, the post-ischemic recovery of cardiac output was maintained and CK leakage was reduced. Next, the effects of 5-(N,N-dimethyl)amiloride (DMA), an inhibitor of Na⁺/H⁺ exchange, were investigated. The inclusion of DMA in the pH 8.2 solution improved the post-ischemic recovery of cardiac output from 12.6±4.1% to 52.0±3.0% (P<0.0001) and reduced cumulative CK leakage during cardioplegic infusions from 38.0±4.0 to 26.1±3.7 IU/45 ml/g dry weight (P=0.044). In contrast, the inclusion of DMA in the pH 6.6 solution provided no added benefit. (Data are expressed as the mean±SEM.) Conclusions: These results suggest that the lesser efficacy of multidose hypothermic cardioplegia in the neonatal rabbit heart may depend on the pH of the cardioplegic solution and is likely to arise, at least in part, from activation of the Na⁺/H⁺ exchanger.     

Economic outcome of off-pump coronary artery bypass surgery: a prospective randomized study

Background. Emphasis on cost containment in coronary artery bypass surgery is becoming increasingly important in modern hospital management. The revival of interest in off-pump (beating heart) coronary artery bypass surgery may influence the economic outcome. This study examines these effects.

Methods. Two hundred patients undergoing first-time coronary artery bypass surgery were prospectively randomized to either conventional cardiopulmonary bypass and cardioplegic arrest or off-pump surgery. Variable and fixed direct costs were obtained for each group during operative and postoperative care. The data were analyzed using parametric methods.

Results. There was no difference between the groups with respect to pre- and intraoperative patient variables. Off-pump surgery was significantly less costly than conventional on-pump surgery with respect to operating materials, bed occupancy, and transfusion requirements (total mean cost per patient: on pump, $3,731.6 ± 1,169.7 vs off-pump, $2,615.13 ± 953.6; p < 0.001). Morbidity was significantly higher in the on-pump group, which was reflected in an increased cost.

Conclusions. Off-pump revascularization offers a safe, cost-effective alternative to conventional coronary revascularization with cardiopulmonary bypass and cardioplegic arrest.     

Prevalence and optimal management strategy for aortic regurgitation in tetralogy of Fallot

Objective: Aortic regurgitation (AR) in the tetralogy of Fallot (TOF) is not frequent, but when present it impacts significantly on surgical management. Furthermore, the incidence of late AR development has been increasing, along with surgical interest in current practices. Methods: Pre- and post-operative studies on 427 patients (TOF, 374; TOF/PA (TOF with pulmonary atresia), 53) who survived corrective operation were reviewed. AR (mild) was detected in 28. Results: Nine had AR preoperatively, while 25 (including six with preoperative AR) exhibited AR post-operatively. In the 19 who developed AR post-operatively, the aortic root diameter (AoRoD) and indexed AoRoD (%AoRoD) were 42±11 mm and 166±36%, increased from the preoperative values of 30±10 mm and 149±24%. AR-free rate at 20 years was 95.1% of all cases studied, 84.3 vs 96.5% in TOF/PA vs classic TOF (P<0.0001), and 82.2 vs 97.0% in bulboventricular VSD vs infracristal VSD (P<0.0001). Older age at repair, and bulboventricular VSD were identified as risk factors for the progression of AR. Aortic valvuloplasty (AVP; n=5) or replacement (AVR; n=4) was performed nine times in eight patients before (n=1), during (n=4), or late after TOF repair (n=4); all showed improvement of NYHA class. Survival- and reoperation-free survival curves showed no significant difference between patients with or without AR. Conclusions: After repair of TOF, careful observation for a late progression of AR is needed for the optimal timing of surgical intervention, especially in patients who repaired at higher age with a dilated aortic root or in patients with bulboventricular VSD.