Effect of hemofiltrated whole blood pump priming on hemodynamics and respiratory function after the arterial switch operation in neonates

Background. Primed blood might have some deleterious effects on neonates during cardiopulmonary bypass (CPB) due to unbalanced electrolytes and inflammatory mediators. We hemofiltrated pump-primed blood before CPB to reduce inflammatory mediators and to adjust pH and the concentrations of electrolytes. The current study investigated the effects of hemofiltrated whole blood priming on hemodynamics and respiratory function after CPB in neonates.

Methods. Patients who underwent the arterial switch operation in the neonatal period for transposition of the great arteries with intact ventricular septum were chosen for this study. Seventeen patients underwent CPB with hemofiltrated blood priming (group HF) and 23 patients underwent CPB with nonhemofiltrated blood priming (group N). The concentrations of electrolytes and bradykinin and high molecular weight kininogen of the primed blood before and after hemofiltration were measured. At 4 hours after completion of CPB, the left ventricular percent fractional shortening, and the relation between the mean velocity of shortening and the end-systolic wall stress (stress velocity index), were measured by echocardiogram in 7 patients in group HF and 6 patients in group N. Alveolar − arterial oxygen tension difference (AaDO₂) and respiratory index (AaDO₂ divided by arterial oxygen tension) were measured at several points for 48 hours after CPB in all patients.

Results. Hemofiltration of the primed blood maintained electrolytes within a physiologic level and significantly reduced the concentrations of bradykinin (5,649 ± 1,353 pg/mL versus 510 ± 35 pg/mL, p < 0.05) and high molecular weight kininogen (52.7% ± 3.2% versus 40.1% ± 3.0% of normal plasma value, p < 0.05). The percent of fractional shortening at 4 hours after completion of CPB was significantly higher in group HF (n = 7) than in group N (n = 6) (22.0% ± 0.7% versus 16.0% ± 0.4%, p < 0.01). There was also a trend toward better stress velocity index in group HF than in group N (0.81 ± 0.81 versus −2.17 ± 0.45, p = 0.09). AaDO₂ and respiratory index were significantly lower in group HF than in group N for 48 hours after CPB, respectively (p < 0.05).

Conclusions. Hemofiltrated fresh whole blood used for CPB priming attenuated cardiac impairment at early reperfusion periods and reduced pulmonary dysfunction in neonates with transposition of the great arteries with intact ventricular septum. This therapeutic strategy may have an advantage in preventing lung and heart dysfunction in pediatric patients who need CPB priming with blood.     

Comparison of the morphologic and vascular reactivity of the proximal and distal radial artery

Background. Variations in the morphology and vascular reactivity of the proximal and distal radial artery might influence its performance as a bypass conduit.

Methods. The morphologic and functional characteristics of the proximal and distal RAs were compared with those of the left and right internal mammary arteries by using histologic and in vitro organ bath techniques.

Results. Proximal RA had a significantly greater medial cross-sectional area compared with that of the distal RA (2.48 ± 0.27 mm² compared with 1.86 ± 0.21 mm², p < 0.05), which were both significantly greater than the left internal mammary artery (0.54 ± 0.09 mm²) or the right internal mammary artery (0.67 ± 0.03 mm²). Proximal RA had a significantly greater response to 90 mmol/L potassium chloride than that of distal RA (88.4 ± 7.3 compared with 60.2 ± 10.3 mN, p < 0.05), and both contracted more than the left internal mammary artery (30.3 ± 2.9 mN) and the right internal mammary artery (32.6 ± 4.1 mN). There was no difference in the response to noradrenaline and adrenaline between proximal and distal RA, both of which contracted more than the left and right internal mammary arteries.

Conclusions. When choosing a segment of RA for use as a bypass conduit, regional variations in biologic properties should be considered.     

Sex and age distribution of 1,25(OH)2D3 receptors in peripheral blood mononuclear cells from normal human subjects

Specific receptors for 1,25 Dihydroxyvitamin D₃ have been described in human peripheral blood mononuclear cells (PBMC). We have tried to find out whether these receptors could show any difference in sex or age distribution. Twenty two healthy men aged 21–66 yr (mean ± SD 41.0 ± 13.6) and nineteen healthy women aged 22–60 yr (38.9 ± 13.9) have been studied. The mean dissociation constant (Kd) was similar in both sexes (1.35 ± 0.70 × 10⁻¹⁰M in males, 1.13 ± 0.66 × 10⁻¹⁰M in females), but the concentration of binding sites (Nmax) was significantly lower in females (2.32 ± 0.92 fmol/10⁷ PBMC vs 4.43 ± 1.38 fmol/10⁷ PBMC in males; p = 0.0001). Neither Kd nor Nmax were significantly correlated with age. No difference was found between pre and postmenopausal women. Further studies are needed to elucidate if this sex difference in PBMC receptors for 1,25 Dihydroxy vitamin D₃ is of any pathophysiological relevance.     

Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open heart operation

Background. Blood cardioplegia (BCP) is widely used for myocardial protection during open heart operation. However, BCP may have a chance to induce neutrophil-mediated myocardial injury during aortic cross-clamping. We clinically evaluated the myocardial protective effect of leukocyte-depleted blood cardioplegia (LDBCP) for initial and intermittent BCP administration in pediatric patients.

Methods. Fifty patients undergoing open heart operation for congenital heart disease between January 1997 and March 1999 were reviewed. Twenty-five were administered LDBCP for myocardial protection during ischemic periods (LDBCP group), and the remaining 25 were given BCP without leukocyte depletion (BCP group).

Results. The difference in plasma concentrations of malondialdehyde between coronary sinus effluent blood and arterial blood just after reperfusion in the LDBCP group (1.68 ± 0.56 μmol/L) was significantly lower than that in the BCP group (2.35 ± 0.62 μmol/L; p < 0.01). The LDBCP group showed significantly lower plasma concentrations of human heart fatty acid-binding protein at 50 minutes after reperfusion (LDBCP group, 103.5 ± 38.7 IU/L; BCP group, 144.8 ± 48.8 IU/L; p < 0.01) and the peak value of creatine kinase-MB during the first 24 postoperative hours (LDBCP group, 17.0 ± 8.5 IU/L; BCP group, 26.0 ± 11.6 IU/L; p < 0.01) than did the BCP group. The maximum dose of catecholamine was significantly smaller in the LDBCP group (LDBCP group, 3.20 ± 2.18 μg · kg⁻¹ · min⁻¹; BCP group, 5.60 ± 2.83 μg · kg⁻¹· min⁻¹; p < 0.01).

Conclusions. These results suggest the usefulness of LDBCP for protection from the myocardial injury that can be induced by BCP administration during aortic cross-clamping.     

Reduced blood loss and transfusion requirements with low systemic heparinization: preliminary clinical results in coronary artery revascularization

In coronary artery revascularization, low systemic heparinization was compared to full systemic heparinization during perfusion with heparin surface-coated cardiopulmonary bypass equipment. Twelve patients were randomly assigned to two groups and perfused with low [activated clotting time (ACT) > 180 s] or full (ACT > 480 s) systemic heparinization. A standard battery of blood samples was taken before the procedure, after heparinization, and at regular intervals during and after cardiopulmonary bypass. No differences were seen between the two groups in regard to age, body surface area, preoperative hematocrit, duration of bypass, bypass hypothermia, cross-clamp time, and number of bypasses per patient. However, there were more internal thoracic artery (ITA) grafts in the group with low systemic heparinization (1.5 ± 0.8 ITA grafts per patient versus 0.8 ± 0.4 ITA grafts per patient with full heparinization; p < 0.05). The oxygenator gradient at the end of perfusion (before weaning) was 107 ± 40 mmHg for low versus 110 ± 10 mmHg for full heparinization (difference not significant). The total amount of heparin used was 7200 ± 1030 IU for low versus 51 400 ± 9700 IU for full (p < 0.05). Postoperative hematocrit was 35.0 ± 2.0% for low versus 24.7 ± 2.7% for full (p < 0.05). Total chest tube drainage was 428 ± 153 ml/m² for low versus 935 ± 414 ml/m² for full (p < 0.05). Homologous transfusions of blood products were necessary in 3/6 patients for low versus 6/6 patients for full (p < 0.10). The total volume of packed red cells transfused was 221 ± 228 ml/m² for low versus 842 ± 366 ml/m² for full (p < 0.05). Final hematocrit at day 7 was 31.0 ± 2.0% for low versus 33.0 ± 3.0% for full (difference not significant). Full systemic heparinization can be avoided during clinical cardiopulmonary bypass by the use of heparin-coated perfusion equipment. A low dose of heparin, similar to the amounts given during vascular surgery, results in reduced blood loss and transfusion requirements.     

Epoxyeicosatrienoic acids (EET(11,12)) may partially restore endothelium-derived hyperpolarizing factor-mediated function in coronary microarteries.

Background. Endothelial cells derive nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The cytochrome P-450–monooxygenase metabolites of arachidonic acid (epoxyeicosatrienoic acids [EETs]) have been suggested to be EDHF. This study was designed to examine the effect of EET_11,12 with regard to the possibility of restoring EDHF function when added into hyperkalemic cardioplegic solution.

Methods. Porcine coronary microartery rings were studied in a myograph. In groups 1 and 2, paired arteries were incubated in either hyperkalemic solution (K⁺ 20 mmol/L) or Krebs’ solution (control). In group 3, the paired arteries were incubated in hyperkalemia plus EET_11,12 (1 × 10^−6.5 mol/L) or hyperkalemia alone (control) at 37°C for 1 hour, followed by Krebs’ washout and then precontracted with 1 × 10^−8.5 mol/L U46619. The EDHF-mediated relaxation to EET_11,12 (group 1) or bradykinin (groups 2 and 3) was studied in the presence of N^G-nitro-l-arginine, indomethacin, and oxyhemoglobin.

Results. After exposure to hyperkalemia, the EDHF-mediated maximal relaxation by bradykinin (72.5% ± 7.8% versus 41.6% ± 10.6%; p < 0.05), but not by EET_11,12 (18.4% ± 3.3% versus 25.1% ± 4.9%; p > 0.05) was significantly reduced. Incubation with EET_11,12 partially restored EDHF function (33.3% ± 9.5% versus 62.0% ± 8.5%; p < 0.05).

Conclusions. In coronary microarteries, hyperkalemia impairs EDHF-mediated relaxation, and EET_11,12 may partially mimic the EDHF function. Addition of EET_11,12 into cardioplegic solution may partially restore EDHF-mediated function reduced by exposure to hyperkalemia.     

Effect of slow-release sodium fluoride on cancellous bone histology and connectivity in osteoporosis

We have previously demonstrated that a treatment regimen of slow-release sodium fluoride (SRNaF) and continuous calcium citrate increases lumbar bone mass, improves cancellous bone material quality, and significantly reduces vertebral fracture rate in osteoporotic patients. In order to assess whether such treatment also improves trabecular structure, we quantitated cancellous bone connectivity before and following 2 years of therapy with SRNaF in 23 patients with osteoporosis and vertebral fractures. In addition, we performed bone histomorphometry on the same sections used for connectivity measurements. There was a significant increase in L2-L4 bone mineral density during therapy (0.827 ± 0.176 g/cm² SD to 0.872 ± 0.166, p = 0.0004). Significant histomorphometric changes were represented by increases in mineral apposition rate (0.6 ± 0.4μm/d to 1.1 ± 0.7, p = 0.0078) and adjusted apposition rate (0.4 ± 0.3 μm/d to 0.6 ± 0.4, p = 0.016). On the other hand, trabecular spacing significantly declined (from 1375 ± 878 μm to 1052 ± 541, p = 0.05). Two-dimensional quantitation of trabecular struts on iliac crest histological sections disclosed significant increases in mean node number per mm² of cancellous tissue area (0.22 ± 0.12 vs. 0.39 ± 0.27, p = 0.0077), the mean node to free-end ratio (0.23 ± 0.21 vs. 0.41 ± 0.46, p < 0.05), and in the mean node to node strut length per mm² of cancellous area (0.098 ± 0.101 vs. 0.212 ± 0.183, p < 0.01). There were no significant changes in any of the measurements associated with free-end number or free-end to free-end strut length. When patients were divided into those with severe and mild-modest spinal bone loss (based upon initial lumbar bone density) the significant changes in connectivity occurred in patients with mild-moderate bone loss, but not in those with severe bone loss, suggesting that fluoride's effect is in part dependent on the presence of a certain critical amount of bone. This finding in combination with the previously reported increases in bone mass and bone material quality may explain the significant reduction in vertebral fracture rate observed with this particular fluoride regimen.     

Heparin-induced platelet dysfunction and cardiopulmonary bypass

Background. Cardiopulmonary bypass is associated with impaired platelet macroaggregation. Heparin contributes to platelet dysfunction before extracorporeal circulation. In vitro heparinization of whole blood does not impair macroaggregation. Heparin releases several endothelial proteins; thus heparin may inhibit macroaggregation indirectly.

Methods. Patients undergoing operations using cardiopulmonary bypass and ABO blood group compatible volunteers were studied. Whole blood impedance aggregometry assessed macroaggregation in response to collagen (0.6 μg ml⁻¹) in blood diluted either with normal saline or with platelet poor plasma, obtained from patients at different stages of cardiopulmonary bypass.

Results. Before heparinization, blood diluted with its own platelet poor plasma recorded an impedance change of 13.0 (4.7 to 15.6) Ohms. Platelet poor plasma obtained after heparinization or during extracorporeal circulation reduced this response to 3.7 (1.1 to 8.4) and 2.0 (1.1 to 3.3) Ohms, respectively (both p < 0.0001 versus pre-heparin; n = 13). Macroaggregation in blood from volunteers was similarly inhibited by patients’ platelet poor plasma (n = 30). The macroaggregatory response in blood sampled after heparinization for cardiopulmonary bypass, decreased gradually from 11.4 (8.2 to 15.9) Ohms immediately after sampling to 1.7 (1.4 to 4.1) Ohms 2 hours later (p < 0.0001; n = 11).

Conclusions. In vivo heparinization induces plasma changes that inhibit platelet macroaggregation. This is an indirect, delayed inhibition that is transferable in vitro to normal platelets.     

Release of S100B during coronary artery bypass grafting is reduced by off-pump surgery

Background. S100B, a plasma marker of brain injury, was compared after coronary artery bypass grafting with and without cardiopulmonary bypass (CPB).

Methods. Fourteen patients with off-pump operations and 18 patients with CPB were compared. Seven patients in the off-pump group underwent a minithoracotomy and received only an arterial graft, whereas 7 patients underwent sternotomy and received both an arterial and one or two vein grafts. S100B was measured in arterial plasma using an immunoassay with enhanced sensitivity.

Results. S100B before the operation was 0.03 μg/L. At wound closure, S100B in patients of the off-pump and CPB groups reached a maximum level of 0.22 ± 0.07 and 2.4 ± 1.5 μg/L, respectively (p < 0.001). No strokes occurred. Patients without CPB receiving arterial and vein grafts released slightly more S100B (p < 0.05) than patients with only arterial grafting. In patients undergoing CPB, S100B increased slightly before aortic cannulation (p < 0.001), to the same level as the maximum reached for the non-CPB group.

Conclusions. Coronary artery bypass grafting with CPB caused a 10-fold greater increase in S100B than off-pump grafting. S100B release after off-pump sternotomy with vein grafting was slightly greater than in arterial grafting through a minithoracotomy.     

Intermittent Antegrade Tepid Versus Cold Blood Cardioplegia in Elective Myocardial Revascularization

Background. The ideal temperature for blood cardioplegia administration remains controversial.

Methods. Fifty-two patients who required elective myocardial revascularization were prospectively randomized to receive intermittent antegrade tepid (29°C; group T, 25 patients) or cold (4°C; group C, 27 patients) blood cardioplegia.

Results. The two cohorts were similar with respect to all preoperative and intraoperative variables. The mean septal temperature was higher in group T (T, 29.6° ± 1.1°C versus 17.5° ± 3.0°C; p < 0.0001). After reperfusion, group T exhibited significantly greater lactate and acid release despite similar levels of oxygen extraction (p < 0.05). The creatine kinase-MB isoenzyme release was significantly lower in group T (764 ± 89 versus 1,120 ± 141 U · h/L; p < 0.04). Hearts protected with tepid cardioplegia demonstrated significantly increased ejection fraction with volume loading, improvement in left ventricular function at 12 hours, and decreased need for postoperative inotropic support (p < 0.05). The frequency of ventricular defibrillation after cross-clamp removal was lower in this cohort (p < 0.05). There were no hospital deaths, and both groups had similar postoperative courses.

Conclusions. Intermittent antegrade tepid blood cardioplegia is a safe and efficacious method of myocardial protection and demonstrates advantages when compared with cold blood cardioplegia in elective myocardial revascularization.     

Outcome with high blood lactate levels during cardiopulmonary bypass in adult cardiac operation

Background. High blood lactate levels during cardiopulmonary bypass (CPB) are associated with tissue hypoperfusion and may contribute to postoperative complications or death. The objective of this study was to determine an association between blood lactate levels during CPB and perioperative morbidity and mortality.

Methods. We reviewed 1,376 patients who underwent cardiac operation with CPB. Patients with abnormal preoperative blood lactate levels were excluded (n = 101). Blood lactate concentration during CPB, clinical data, and perioperative events were recorded.

Results. Peak blood lactate levels of 4.0 mmol/L or higher during CPB were present in 227 patients (18.0%). Postoperative mortality was higher in this group than in the patients who had peak blood lactate levels of less than 4.0 mmol/L during CPB (11.0% versus 1.4%; p < 0.001, relative risk [RR] = 9.0). Postoperative hemodynamic instability occurred in 29.5% of patients with elevated levels of lactate during CPB compared with 10.9% of patients with lower lactate levels (p < 0.001, RR = 3.4). Overall, major postoperative complications occurred in 43.2% and 21.8% of patients in each group, respectively (p < 0.001, RR = 2.7). Logistic regression analysis revealed that peak blood lactate levels of 4.0 mmol/L or higher during CPB were strongly associated with postoperative mortality (p = 0.0001) and morbidity (p = 0.013).

Conclusions. Blood lactate concentration of 4.0 mmol/L or higher during CPB identifies a subgroup of patients with increased risk of postoperative morbidity and mortality.     

Anaphylactic/anaphylactoid reactions during cardiac surgery

Over a 12-month period, 1,743 patients were retrospectively evaluated for anaphylactic/anaphylactoid reactions during cardiac surgery. Reactions to protamine, vancomycin, blood, and metocurine were observed in eight patients (0.46%). Base-line to reaction mean arterial pressures decreased from 81 ± 9 mmHg to 50 ± 7 mmHg (mean ± SD; p < 0.001), cardiac output increased from 4.6 ± 0.6 L/min to 6.5 ± 1.2 L/min (p < 0.005), stroke volume increased from 49 ± 11 to 83 ± 22 ml/beat (p < 0.02), and systemic vascular resistance decreased from 1,294 ± 137 to 563 ± 127 dyne/sec/cm⁻⁵ (p < 0.001). Two patients developed pulmonary artery hypertension, while only one patient developed bronchospasm. Initial hypertnsion during anaphylacticlanaphylactoid reactions is due to decreased systemic vascular resistance, not myocardial depression.     

Heart surgery with extracorporeal circulation leads to platelet activation at the time of hospital discharge

Objective: Heart surgery with extracorporeal circulation has a marked effect on platelet function and coagulation accounting for abnormal blood loss and allegedly a low incidence of thromboembolic complications. Little is known about platelet function at the time of hospital discharge of routine patients. Methods: Blood samples from 91 patients undergoing elective heart surgery were drawn before surgery and prior to discharge. Thirty-seven patients underwent coronary artery surgery and 54 an aortic valve implantation. The mean age of patients was 69±9 years. Fifty patients were male and 41 female. Platelet function was evaluated using plasma β-thromboglobulin quantification in enzyme-linked immunosorbent assay. In addition, flow cytometric analysis of platelet–monocyte conjugates and platelet–neutrophil conjugates was performed. Results: The platelet count before discharge was significantly increased (265±86 vs. 212±61×10⁹/l preoperatively). β-Thromboglobulin was significantly increased (176±127 vs. 79±70 ng/ml preoperatively) and flow cytometry proved a significant increase in monocyte–platelet aggregates (8.3±5.4% vs. 5.3±2.6% preoperatively) indicating platelet activation at the time of hospital discharge. There were no significant differences among the three subgroups coronary surgery, mechanical valve insertion and biological valve insertion. Conclusions: Heart surgery with extracorporeal circulation leads to significant platelet activation and a reactive increase in platelet count before discharge. This is in contrast to the reduced platelet function immediately postoperatively.     

Osteocyte density in aging subjects is enhanced in bone adjacent to remodeling haversian systems

The osteocyte is a candidate regulatory cell for bone remodeling. Previously, we demonstrated that there is a substantial (approximately 50%) loss of osteocytes from their lacunae in the cortex of the elderly femoral neck. Higher occupancy was evident in tissue exhibiting high remodeling and high porosity. The present study examines the distribution of osteocytes within individual osteonal systems at differing stages of the remodeling cycle. In 22 subjects, lacunar density, osteocyte density, and their quotient, the percent lacunar occupancy, was assessed up to a distance of 65 μm from the canal surface in six quiescent, resorbing, and forming osteons. In both forming (p = 0.024) and resorbing (p = 0.034) osteons, osteocyte densities were significantly higher in cases of hip fracture than controls. However, there were no significant between-group differences in lacunar occupancy. In both cases and controls, osteocyte density (p < 0.0001; mean difference ±SEM: 157 ± 34/mm²) and lacunar occupancy (p = 0.025; mean difference: 8.1 ± 3.4%) were shown to be significantly higher in forming compared with quiescent osteons. Interestingly, resorbing systems also exhibited significantly elevated osteocyte density in both the fracture and the control group combined (mean difference 76 ± 23/mm²; p = 0.003). Lacunar occupancy was also greater in resorbing compared with quiescent osteons (both groups combined: p = 0.022; mean difference: 5.7 ± 2.3%). Elevated osteocyte density and lacunar occupancy in forming compared with quiescent systems was expected because of the likely effects of aging on quiescent osteons. However, the higher levels of these parameters in resorbing compared with quiescent systems was the opposite of what we expected and suggests that, in addition to their postulated mechanosensory role in the suppression of remodeling and bone loss, osteocytes might also contribute to processes initiating or maintaining bone resorption.     

Pharmacologically induced preconditioning with diazoxide: a novel approach to brain protection

Background. Ischemic preconditioning is an endogenous mechanism whereby brief periods of ischemia render neurons resistant to subsequent lethal insults. This protection appears to alter cellular apoptosis and can be induced by potassium channel openers acting on the inner membrane of the mitochondria (mitoK_ATP). To test the hypothesis that pharmacologic preconditioning could provide neuroprotection, the mitoK_ATP opener diazoxide was used in a canine model of brain injury induced by hypothermic circulatory arrest (HCA).

Methods. Seventeen dogs were placed on cardiopulmonary bypass (CPB) and cooled to 18°C. After 2 hours of HCA, animals were rewarmed and weaned from CPB. Six dogs received intravenous diazoxide (2.5 mg/kg bolus 15 minutes prior to CPB, then 0.5 mg/min until circulatory arrest, then restarted for the first hour of rewarming). Six animals received vehicle only. Five received diazoxide and the mitoK_ATP blocker 5-hydroxydecanoate (5-HD). Using a modified Pittsburgh Canine Neurological Scoring System (0 = normal, 500 = brain death), animals were evaluated every 24 hours for 3 days. The brains were removed and histologic sections of four regions characteristically injured in this model were scored (0 = no injury, 4 = infarction) by a neuropathologist in a blinded fashion.

Results. Clinical scoring showed marked improvement in the diazoxide group at 48 hours (101 ± 10.5 vs 165 ± 14.8, p < 0.01) and 72 hours (54 ± 9.3 vs 137 ± 12.1, p < 0.01). This neuroprotection was attenuated when 5-HD was concomitantly administered. Three of four brain regions typically injured in this model (cortex, hippocampus, and entorhinal cortex) had significant neuron preservation in the diazoxide group. Likewise, combined region scores were significantly improved in the treatment group (1.18 ± 0.2 vs 2.46 ± 0.2, p < 0.01).

Conclusions. Pretreatment with diazoxide resulted in significant improvement in both clinical neurologic scores and histopathology in our model of HCA. This suggests that pharmacologic preconditioning with the mitoK_ATP channel opener diazoxide may offer effective neuroprotection during HCA.     

Heat shock improves recovery and provides protection against global ischemia after hypothermic storage

Background. Improved methods of donor heart preparation before preservation could allow for prolonged storage and permit remote procurement of these organs. Previous studies have shown that overexpression of heat-shock protein 72 provides protection against ischemic cardiac damage. We sought to determine whether rats subjected to heat stress with only 6-hour recovery could acquire protection to a subsequent heart storage for 12 hours at 4°C.

Methods. Three groups of animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats (whole-body hyperthermia 42°C for 15 minutes). After 12-hour cold ischemia hearts were reperfused on a Langendorff column. To confirm any differences in functional recovery, hearts were then subjected to an additional 15-minute period of warm global ischemia after which function and lactate dehydrogenase enzyme leakage were measured.

Results. Heat-shocked animals showed marked improvements compared with controls in left ventricular developed pressure (63 ± 4 mm Hg versus 44 ± 4 mm Hg, p < 0.05) heart rate × developed pressure (13,883 ± 1,174 beats per minute × mm Hg versus 8,492 ± 1,564 beats per minute × mm Hg, p < 0.05), rate of ventricular pressure increase (1,912 ± 112 mm Hg/second versus 1,215 ± 162 mm Hg/second, p < 0.005), rate of ventricular pressure decrease (1,258 ± 89 mm Hg/second versus 774 ± 106 mm Hg/second, p < 0.005). Diastolic compliance and lactate dehydrogenase release were improved in heat-shocked animals compared with controls and sham-treated animals. Differences between heat-shocked animals and control or sham-treated animals were further increased after the additional 15-minute period of warm ischemia. Western blot experiments confirmed increased heat-shock protein 72 levels in heat-shocked animals (> threefold) compared with sham-treated animals and controls.

Conclusions. Heat shock 6 hours before heart removal resulted in marked expression of heat-shock protein 72 and protected isolated rat hearts by increased functional recovery and decreased cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of heart preservation for transplantation. Protection was further confirmed after an additional 15-minute period of warm ischemia.     

Intraaortic Balloon Counterpulsation Improves Right Ventricular Failure Resulting From Pressure Overload

Background. Right ventricular (RV) dysfunction is common after heart transplantation, and myocardial ischemia is considered to be a significant contributor. We studied whether intraaortic balloon counterpulsation would improve cardiac function using a model of acute RV pressure overload.

Methods. In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres.

Results. After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 ± 2 to 60 ± 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 ± 4 to 49 ± 2 mm Hg; p < 0.01), RV ejection fraction (0.51 ± 0.04 to 0.16 ± 0.02; p < 0.01), and cardiac index (2.48 ± 0.04 to 1.02 ± 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 ± 2 to 61 ± 3 mm Hg; p < 0.01), cardiac index (1.02 ± 0.11 to 1.45 ± 0.14; p < 0.05), RV ejection fraction (0.16 ± 0.02 to 0.23 ± 0.02; p < 0.01), and blood flow to the left ventricle.

Conclusions. In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.     

Preliminary experience with the St. Jude Medical Regent mechanical heart valve in the aortic position: early in vivo hemodynamic results

Background. The St. Jude Medical Regent is a new generation mechanical aortic valve.

Methods. Between March 2000 and July 2001, this valve was implanted in the aortic position in 40 patients (21 men; mean age 59.1 ± 9.0 years). Preoperatively, 24 patients (60%) were in New York Heart Association functional class III or IV. Eighteen patients (45%) underwent associated procedures. Mean valve size was 21.4 ± 2.4 mm. The mean duration of follow-up was 8.5 ± 4.5 months (range, 1 to 16 months).

Results. There were no operative deaths. Early complications included one reoperation for bleeding and one transient low output syndrome. Valve replacement was followed by a significant reduction in mean and peak transaortic gradients over time (p < 0.001) and analysis of variance failed to demonstrate statistical differences between valve size over time (p = not significant). A significant reduction in left ventricular hypertrophy occurred over time (p = 0.01) in all valve sizes (p = not significant between groups): baseline left ventricular mass index was 194 g/cm²; it reduced by 22 g/cm² (p = 0.006) at discharge. Left ventricular mass index decreased from 172 ± 55 g/cm² to 156 ± 44 g/cm² (p = 0.03) from discharge to 2 months. Further reductions were not significant. Relative wall thickness decreased from 0.57 ± 0.13 preoperatively to 0.42 ± 0.06 at discharge (p = 0.001), and again at 2 months (−0.2; p = not significant), and at 1 year (−0.02; p = not significant).

Conclusions. The early experience with the St. Jude Medical Regent valve has been satisfactory.     

Brain Damage and Myocardial Dysfunction: Protective Effects of Magnesium in the Newborn Pig

Background. Brain damage is associated with myocardial dysfunction resulting from excessive release of endogenous catecholamines and Ca²⁺ overload. Magnesium ion, a natural Ca²⁺ blocker, has recently been recognized as a myoprotective agent.

Methods. Myocardial function was assessed in 3- to 7-day-old piglets from pressure–volume data (obtained by the conductance catheter/micromanometer technique) before and for 4 hours after ligation of the aortic arch vessels and was correlated with ultrastructural changes. Group a (n = 6) received MgSO₄ immediately after induction of brain damage for 4 hours, whereas group b (n = 6) did not receive MgSO₄ and served as control.

Results. In both groups after induction of brain damage, there was a significant (p < 0.05) increase in end-systolic elastance and preload-recruitable stroke work that persisted for 1 hour. However, after 2 and 4 hours, there was a significant (p < 0.05) reduction in both variables in group b (end-systolic elastance, 74% ± 5% and 59% ± 6%, respectively, and preload-recruitable stroke work, 77% ± 4% and 64% ± 3%, respectively, compared with baseline), and in group a, the values returned to baseline. The chamber stiffness index rose significantly (p < 0.05) in group b 15 minutes after induction of brain damage and remained significantly (p < 0.05) higher for 4 hours versus no significant change in group a. Plasma levels of epinephrine and norepinephrine were similar in the groups before and after brain damage. Electron microscopic study showed severe ultrastructural changes in group b and significantly milder changes in group a.

Conclusions. We conclude that MgSO₄ may protect the neonatal myocardium when administered immediately after brain damage.     

Effects of cerivastatin on vascular function of human radial and left internal thoracic arteries

Background. Statins may enhance vascular function independently of effects on cholesterol. This study investigated the ability of statins to modulate the vascular recovery of arteries used as coronary bypass grafts.

Methods. Specimens of radial artery and left internal thoracic artery were obtained during coronary artery bypass grafting. The specimens were divided into vascular rings, which were incubated in the absence or presence of cerivastatin (10⁻⁶ mol/L) for either 2 or 24 hours. Using an organ bath technique, endothelial function was examined using acetylcholine (10⁻⁹ to 10⁻⁵ mol/L) after contraction by 3×10⁻⁸ mol/L of endothelin-1.

Results. Time-related endothelial dysfunction was shown in the control group of radial artery but not in the cerivastatin group: maximal endothelium-dependent vasodilation in the control and cerivastatin groups were 56.8% ± 10.2% and 65.9% ± 10.1% at 2 hours and 39.4% ± 4.7% and 68.4% ± 5.0% (p < 0.01, vs control) at 24 hours, respectively. On the other hand, in the left internal thoracic artery, those in the control and cerivastatin groups were 38.3% ± 8.2% and 45.0% ± 5.5% at 2 hours and 38.1% ± 8.2% and 56.5% ± 8.8% at 24 hours, respectively (NS).

Conclusions. In radial artery, cerivastatin significantly preserved endothelium-dependent vasodilation, which diminished with time in the control group. This could have very important implications in the clinical practice of coronary artery bypass grafting.